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López-Cepeda, L.;  Castro, J.D.;  Aristizábal-Pachón, A.F.;  González-Giraldo, Y.;  Pinzón, A.;  Puentes-Rozo, P.J.;  González, J. Astroglial sncRNA Relevance on Early Neurodegeneration Stages. Encyclopedia. Available online: https://encyclopedia.pub/entry/33107 (accessed on 21 July 2024).
López-Cepeda L,  Castro JD,  Aristizábal-Pachón AF,  González-Giraldo Y,  Pinzón A,  Puentes-Rozo PJ, et al. Astroglial sncRNA Relevance on Early Neurodegeneration Stages. Encyclopedia. Available at: https://encyclopedia.pub/entry/33107. Accessed July 21, 2024.
López-Cepeda, Leonardo, Juan David Castro, Andrés Felipe Aristizábal-Pachón, Yeimy González-Giraldo, Andrés Pinzón, Pedro J. Puentes-Rozo, Janneth González. "Astroglial sncRNA Relevance on Early Neurodegeneration Stages" Encyclopedia, https://encyclopedia.pub/entry/33107 (accessed July 21, 2024).
López-Cepeda, L.,  Castro, J.D.,  Aristizábal-Pachón, A.F.,  González-Giraldo, Y.,  Pinzón, A.,  Puentes-Rozo, P.J., & González, J. (2022, November 04). Astroglial sncRNA Relevance on Early Neurodegeneration Stages. In Encyclopedia. https://encyclopedia.pub/entry/33107
López-Cepeda, Leonardo, et al. "Astroglial sncRNA Relevance on Early Neurodegeneration Stages." Encyclopedia. Web. 04 November, 2022.
Astroglial sncRNA Relevance on Early Neurodegeneration Stages
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Astrocyte dysfunction with consequential neuronal microenvironment dysregulation (astrocytopathy) has been involved in processes of early neurodegenerative disease. Small non-coding RNA (sncRNA) vary in different detrimental conditions of Central Nervous System (CNS), and sustained changes in sncRNA astrocyte expression profile can be the consequence of these conditions. sncRNA signatures derived from astrocytes, could therefore be a key to reveal early neurodegenerative disease, helping to unravel the astrocyte role in neurodegenerative disease. Current biomarkers for neurodegenerative disease, face strong challenges such as high variability, negative cost-effectiveness, low availability, or invasiveness. For example, cerebrospinal fluid evaluation (CSF tests) is a highly invasive, expensive, risky procedure, often used in the diagnosis of neurodegenerative disease. The alternative to CSF tests, which is neuroimaging requires especial equipment, long operating time and it is highly expensive making their widespread use prohibitive. Still, misdiagnosis could occur after the use of these powerful tools. Therefore, new methods are needed to assess neurodegeneration, and extracellular vesicles from astrocytes (ADEV) represent and interesting target of research. ADEV cross blood brain-barrier (BBB) carrying sncRNA from astrocytes and cell-specific membrane surface proteins, which can be used to allow ADEV separation from vesicles of other sources and other contaminants. This approach could be useful for the analysis of a less invasive, simpler, peripheral sample of blood origin. sncRNA dysregulated in conditions associated with increased risk of neurodegenerative disease and their possible effects on target cells is shown.

Astrocyte Derived Extracellular Vesicles (ADEVs) small non-coding RNA (sncRNA) sncRNA transcriptome (sncRNome) circulating sncRNA extracellular sncRNA

1. Introduction

Neurodegenerative diseases are caused by a general dysfunction of the Central Nervous System (CNS), characterized by progressive loss of neuron structure and function[1]. In recent years, neurodegenerative diseases have become a global public health problem due in part to the increase in the elderly population in both developed and under developing countries. Pathologies such as Alzheimer’s disease (49–65%) [2][3], Parkinson’s disease (15%) [2], Vascular Dementia and Multiple Sclerosis, among others, are included within the ND. Environmental factors play an essential role in the etiology of neurodegenerative diseases and sporadic origin is dominant; vascular dementia is an acquired disease, and sporadic cases represent more than 95% of Alzheimer’s disease, 90% of Parkinson’s disease and 80% of Multiple Sclerosis [4][5][6]. Diagnosis of neurodegenerative diseases is made difficult by lack of precision and it is based in the analysis of clinical history (mainly through cognitive and motor neurological examination) [7][8], and paraclinical assessment that includes neuroimaging, and Cerebrospinal Fluid (CSF) evaluation [8][9][10]. Clinical assessment depends on symptoms, often not so apparent [7], and often it is prone to bias and lack of accuracy.

Another characteristic of neurodegenerative diseases diagnosis is the complexity associated with paraclinical assessment which troubles timely diagnosis. Detection of distinct hallmarks of neurodegenerative diseases has been possible with neuroimaging and CSF evaluation up to very early time points before symptoms onset (~30 years) [11]. However, invasiveness, low availability, and risk associated with CSF measures [11], and high costs, long operating time, and inaccessibility associated with neuroimaging [8][12], limits the widespread use of these markers. Moreover, the presence of this alterations is not enough for diagnosis. Such a situation limits the success and the extent of therapies and treatments [11][13][14][15], but it is also an opportunity for simpler peripheral biomarkers which are preferred due to their lower invasiveness, risk, and complexity [16]. In support of this view successful CSF or neuroimaging biomarkers have been evaluated in peripheral fluids such as blood, saliva, plasma, serum, and tears, but markers showing promising results in CSF and neuroimaging require ultrasensitive techniques for peripheral evaluation due to reduced concentration and cross-reactivities [8]. Still with biosensor detection down to femtomolar levels [17], fluctuations non associated with disease also affect biomarker performance [18][19][20]. Recently, composite measurements of biomarkers (e.g., t-tau/Aβ42, p-tau/Aβ42, Aβ42/Aβ40) have improved the precision of peripheral based biomarkers[17], but there remains an urgency for the development of simpler cost-effective biomarkers for the detection of neurodegenerative diseases in early neurodegeneration stages [11][15].

Astrocytes regulate central processes for neuronal microenvironment maintenance, protection, and repair [21][22], including neuroinflammation [23], which is a hallmark in most neurodegenerative deseases. Depending on severity or duration an insult/injury can lead to astrocyte dysfunction either by impairment of the normal process or by gain of an abnormal function (astrogliosis), which could trigger neurodegeneration by neuronal microenvironment dysregulation (a process termed astrocytopathy) [24]. Astroglial pathology has been detected before symptoms onset in various neurodegenerative diseases [25][26][27]. Hence astrocyte dysfunction constitutes a target for early neurodegeneration biomarker research. A variety of glial-derived substances such as DJ-1, CCL2, CCL7, CXCL10, interleukins (IL-1β, IL-2, IL-6, IL-8, IL-12, IL-18), and CRP [16][28] have been studied with diagnostic interest. Interestingly some of them have shown diagnostic potential in peripheral tissues such as plasma for Alzheimer’s disease or tears for Parkinson’s disease [16][28], and it is likely that these testing become routine screening target for neurodegenerative diseases early diagnosis.

2. Astrocyte Relevance on Early Neurodegeneration Stages

Neurodegenerative disease (ND) etiology is particularly difficult to define, for instance Aβ peptides, which are the most representative hallmark of Alzheimer’s disease, have been observed to reduce oxidative stress in some circumstances, blurring the limits between pathological and physiological changes [29], therefore neurodegenerative diseases onset is highly heterogeneous, undefined, and not well understood [30], and early phases of neurodegenerative diseases difficult to define. Early neurodegeneration stages can be defined in two well separate phases that vary between diseases: preclinical and prodromal [7][20][30]. Preclinical phases can be further partitioned in pre-symptomatic and early symptomatic, while the prodromal stage is characterized by symptoms not strong enough to consider a diagnosis but clearly evidenced in clinical settings [11]. Astrocyte dysfunction appears in early phases of Alzheimer’s disease, and early Parkinson’s disease (<5 years of disease), as imaged in vivo by positron emission tomography (PET) of 11C-deuterium-L-deprenyl (11C-DED) and 11C-BU99008, respectively both of which recognize reactive astrocytes [31][32]. 11C-DED has been observed in mild cognitive impairment [31], and the astrocytic enzyme targeted by this ligand which is monoamine oxidase B (MAO-B) is a promissory biomarker in Multiple Sclerosis [32]. Therefore, astrocyte dysfunction biomarkers should identify early neurodegeneration stages in most neurodegenerative diseases before extensive neuronal damage occurs.

Astrocytes perform multifold functions some of them essential such as regulating electrochemical balance, distributing the energy uptake (meeting the high energy requirement of neurons), and accelerating detoxification which protect neurons from oxidative damage [22]. Several papers summarize astrocyte general functions and in specific contexts such as innate immunity, inflammation, and neuroprotection [21][33][34][35][36]. Astrocytes respond to CNS injury/lesion with the activation of a complex heterogenous response termed astrogliosis [24], which can lead to the activation of pivotal processes for neurodegenerative diseases such as neuroinflammation. Since astrogliosis modifies astrocytic function (sometimes permanently), neurodegeneration can start because of both, the reduction of essential functions performed by astrocytes and an exacerbated astrocytic activity (abnormal gain of function), this is formally called astrocytophaty [24]. Growing evidence supports that astrocyte dysfunction is sufficient by itself to start secondary neurodegenerative process in early neurodegenerative stages of different neurodegenerative diseases.

For instance, in Alzheimer Disease abnormal astrocyte exposure to saturated fatty acids such as stearic, linoleic, oleic and palmitic acid has been linked with higher risk [37][38]. High exposures of human astrocytes to palmitic acid decreased cell viability and mitochondrial membrane potential, also producing autophagy impairment, proinflammatory cytokine overproduction (IL-1β, IL-6 and TNF-α), endoplasmic reticulum stress, and morphological changes associated with dysfunction [39][40][41]. Furthermore, neuron exposition to equivalent concentrations of palmitic acid did not generate the same effect [38][42], but when neurons were exposed to media from astrocytes induced with palmitic acid toxicity, hyperphosphorylation of tau [38], and induction of Aβ peptide production was observed [43]. Both marks associate with onset of Alzheimer’s disease and appear in early neurodegeneration stages [11][44].

Animal models and human also support in vitro observations situating astrocyte dysfunction as an early pathological event in Alzheimer’s disease. In animal models, High Fat Diet robustly induced cognitive impairment in healthy rat [45] and Tg2576 mouse mutant APP model of Alzheimer’s disease [46]. Tg2576 mouse also showed higher production of amyloidogenic Aβ peptides and higher γ secretase activity after High Fat Diet [46], as well as some contradictory results with improved cognitive functions and no Aβ significant burden in some studies [47]. Alterations in the fatty acid composition seem to be responsible for these contradictions [47] but sex differences could be also responsible because study with contradictory results did not account for animal sex [47]. In general, metabolic disorder models (including High Fat Diet) caused alterations in neuroinflammation and BBB function (processes key controlled by astrocytes) in both animal models (including zebra fish) and humans [48]. Lastly, high-glycemic-load diet exposure of healthy humans caused higher Aβ burden measured by PET and an increasing saturated fatty acids concentration associated with progression to Alzheimer’s disease in human serum and brain tissue [37], therefore helping to explain relationship between dyslipidemia and related metabolic disorders with Alzheimer’s disease and recapitulating in vitro observations.

Parkinson’s Disease development is partly due to astrocyte dysfunction with evidence building up to suggest early astroglial participation in neuroinflammation and in the disruption of several neuroprotective mechanisms as partly initiator events [49]. Several of the 19 genes causative genes of mendelian forms of Parkinson’s disease, express in equal amount in astrocytes than in neurons, with GBA, EIF4G1, VPS35, FBXO7 and PINK1, showing higher expression in astrocytes than in neurons [49][50]. Mutations of these genes in astrocytes have been shown to disrupt lipid metabolism, proliferation, glutamate uptake, cytokine regulation, neurotrophic signaling, anti-inflammatory secretion, and therefore a role in early phases of disease is possible [49]. Animal models of Parkinson’s disease have also shown increased expression of GFAP, neuroinflammation and onset of astrogliosis before motor symptoms [49][51]. Induced by neurotoxin 6-hydroxydopamine and rotenone Parkinson’s disease models also displayed earlier neurodegeneration and neuroprotection diminishment concomitant with astroglial dysfunction in astrocyte conditional mutation [49].

Efforts in Vascular Dementia early detection center in the identification of subclinical symptoms of cerebrovascular conditions that precede this condition, since a stroke constitute a risk marker by itself. Most vascular dementia cases arise after vascular damage caused by smaller and less evident pathophysiological lesions such as lacunar infarct [52]. In most cases such lesions are detected by neuroimaging and therefore there remains cost and accessibility issues for their widespread use, however alternatives of detection such as neurological tests have been proposed [53]. Combined protein detection of CRP, homocysteine and Toll-like receptor 4 (TLR4) in serum have shown biomarker value for cognitive abnormalities related with Cerebral Small Vessel Disease which is the most common vascular abnormality associated with vascular dementia [54]. Evidence shows that these preceding vascular abnormalities induce changes in astrocyte function, including astrocyte activation, end-foot disruption, and EAAT2 and AQP4 downregulation. homocysteine induced vascular dementia mouse model similarly showed astrocytic end-foot disruption concomitant to AQP4 downregulation with astrogial activation, and these astrocytic changes took place in a symptomatic phase (cognitive deficits measured in mice) after microglial activation [52]. This evidence shows that measuring astrocytic functional changes could have a biomarker value in specific stages of vascular dementia with microglial changes being more relevant for early detection, but it requires further research and other models of vascular dementia to confirm these observations.

In Multiple Sclerosis, astrocyte dysfunction takes place before the glial scar formation, previously believed to be the earliest phase in which astrocyte dysfunction took place. Evidence shows that, before lesion demyelination, astrocytes contribute to the inflammatory response that results in the recruitment of lymphocytes and regulate BBB and BSCB permeability to favor lesion [55]. Evidence in preclinical model of experimental autoimmune encephalomyelitis strongly support astrocyte dysfunction role in early phases of Multiple Sclerosis disrupting BBB, BSCB and promoting lymphocyte recruitment. Astrocyte-specific CCL2 deletion (a central gene in BBB disruption) in mouse ameliorated Multiple Sclerosis in experimental autoimmune encephalomyelitis [23][55]. Furthermore lactosylceramide, an activator of CCL2 and powerful inflammatory molecule, is overexpressed in astrocytes of the experimental autoimmune encephalomyelitis model and its inhibition suppressed neurodegeneration [55][56]. In humans, it has been found that genetic risk factors of Multiple Sclerosis cause a strong in vitro probed effect in astrocyte function that increases NF-κB signaling and chemokine liberation, which can be related with lymphocyte recruitment in prodromal stages. In addition, astrocytes perform neuroprotective roles in Multiple Sclerosis such as the recruitment of microglia in damaged myelin clearance to favor lesion repair [55] that may take place in symptomatic phases of the disease.

Several conditions, neurological disorders, and lesions that associates with increased risk of neurodegenerative diseases cause alterations in astrocyte function, which could precede neurodegenerative disease. A proinflammatory microenvironment, oxygen and glucose deprivation, intracerebral hemorrhage, traumatic brain injury, Postoperative Cognitive Dysfunction and ethanol exposure, represent conditions inducing increased risk of neurodegenerative diseases [37][52][57][58][59][60]. Neurovascular unit astrocytes suffer atrophy of end-foot processes under ischemia, traumatic brain injury, brain contusion and neurodegenerative diseases [52][61], while morphine induces neuroinflammation and permanent cognitive deficit in a Postoperative Cognitive Dysfunction rat model [58][60], in which astrocyte mediated activation of microglia possibly initiates the insult [58]. Furthermore, rat models demonstrate Parkinson’s disease -like deficits in motor function after repeated cycles of binge-like ethanol intake [62]. Independently of the origin, astrocyte dysfunction generates changes in their secretory profile, this includes the sncRNA from Astrocyte Derived Extracellular Vesicle (ADEV). This fraction contributes to total extracellular vesicle derived sncRNA, which is the most studied source of extracellular sncRNA that has been evaluated in neurodegenerative diseases [58][63][64][65][66][67]. However, to the researchers' knowledge, there are no studies yet that had separately analyzed individual astrocyte-specific sncRNA signatures in human sample in early neurodegeneration stages. Table 1 shows sncRNA from ADEV found dysregulated in conditions associated with early neurodegeneration and neurodegenerative diseases risk in human, mouse, and rat models. These conditions include Il-1β and TNF-α stimulus [63], Hypoxic-Ischemic Brain Damage [68], ischemic preconditioning [65], SOD1 mutation [69], ethanol induced cell toxicity, and morphine-mediated neuroinflammatory microenvironment which is associated with Postoperative Cognitive Dysfunction [58]. As the table shows, astrocyte-specific circulating sncRNA could change in response to early neurodegenerative processes making early neurodegeneration associated with astrocyte dysfunction identifiable.

Table 1. Astrocyte Derived Extracellular Vesicle (ADEV) derived sncRNA dysregulated in conditions associated with increased risk of neurodegenerative disease (NDD) and their possible effects on cell targets based on evidence in human, as well on rat and mouse models. The third column specifies the change in expression favored by conditions associated with increased risk of NDD. ALS: Amyotrophic lateral sclerosis, ASCI: Acute Spinal Cord Injury, CRC: colorectal cancer, EAE: Experimental Autoimmune Encephalomyelitis, HAND: HIV associated neurocognitive disorders, HFD: High-fat diet, HIBD: Hypoxic-Ischemic Brain Damage, IBZ: Ischemic Boundary Zone, NPC: Neural Progenitor Cells, OSA: Obstructive Sleep Apnea, PASMCs: Pulmonary Artery Smooth Muscle Cells, pMCAO: permanent Mid Cerebral Artery Occlusion, SMA: Spinal Muscular Atrophy, SCI: Spinal Cord Injury, TBI: Traumatic brain Injury.

sncRNA

Condition

Role Associated with Early Neurodegeneration Conditions or Risk of Neurodegeneration

Role in Neurodegenerative Disease or Effects in CNS Cells

Additional Roles and Effects in Peripheral Cells

Let-7f

Il-1β stimulation, ischemia

Upregulated in ADEV after Il-1β stimulation in primary rat astrocytes [63], upregulated in rat pMCAO ischemia model after lesion [70]

Sporadic ALS downregulated biomarker [71], upregulated in AD hippocampus [72]. Targets involved in FoxO and MAPK signaling pathways and apoptosis [71]. Increased after HFD in rat [73]. •

Promotes differentiation in rat neural stem cells [74]. Downregulates NDRG3 expression in rat cortical neurons to regulate hypoxia response (proapoptotic) [70]. ‡

Activate TLR7 [75]. ⁑

Downregulated in glioma cell lines, inhibits proliferation and migration, increases apoptosis [76]. ∞ *

Protection against oxidative damage [77]. ∞ ‡

Tumor suppressor miRNA, targets the aromatase gene (CYP19A1) [78]. ∞

miR-16-5p

SCI, TBI, Il-1β and TNF-α stimulation

Upregulated in ADEV after Il-1β and TNF-α stimulation in primary rat astrocytes [63]. Upregulated in rat tissue after SCI [79]. Downregulated in human serum and mouse model after TBI [80].

Biomarker, dysregulated in ALS serum, showed lower expression in slower progressing ALS [81]. Key implication in subacute stage of SCI [82]. •

Reduce dendritic complexity and growth, spike rates and burst activity after inflammatory stimulus. Downregulates NTRK3 and Bcl2 [63]. Stimulates apoptosis and inflammatory proteins, Targets Apelin-13 inactivating ERK1/2 pathway [79]. ‡

Increases apoptosis, causes inflammation [83]. ⁑

Downregulated in glioma cell lines, targets TLN1 to increase glioma viability, proliferation, migration and invasion after TIIA [84]. ∞ *

Decreases fracture healing. Negatively regulates Bcl-2 and Cyclin-D1, therefore suppressing osteogenic differentiation, and osteoblast proliferation and survival. Inhibited proliferation promoting cell-cycle arrest and apoptosis [80]. π

miR-17-5p

OGD, HIBD

Downregulated in ADEV after HIBD in rat [68].

Potential regulator of robust differentially expressed genes causing downregulation of GABAergic synapse and signaling pathways in AD [85]. It also counter IRE1a pathway downregulating TXNIP, NL3P inflammasome activation and Il-1β production [86]. Reduces inflammation related proteins after HIBD with lower production of TNF-α and IL-1β [68]. •

Reduces neuronal death and apoptosis after HIBD [68]. ‡

Promotes proliferation of activated astrocytes after SCI [87]. *

Upregulated in AD, in microglia adjacent to Aβ deposits. Targets autophagy receptor NBR1 inhibiting clearance of Aβ [88][89]. ⁑

Targets APP expression [90], BNIP2, SOD, GSH-Px and CAT expression, and reduces apoptosis and inflammation after OGD [68]. ∞ ⁑

Expression increased after myocardial infarction. Inhibition associated with cardiomyocyte survival through STAT3 targeting [91]. γ

Promotes osteoclastogenesis via targeting PTEN [92]. Promotes osteogenic differentiation and ossification, and cytokines such as VEGF [93]. π

Upregulated in various cancers, Reduced proliferation in GIST tissue samples, targets KIT expression [94]. ∞

mir-21

Ischemia

Identified in ADEV from ALS mSOD1 mouse model with neurodegeneration stage not specified, upregulated [69]. Overexpressed in hippocampus after ischemia in rat [95].

Reduced expression in axons in alcoholism and depression [96]. Suppresses OGD induced apoptosis, and Faslg pro-apoptotic factor levels. Upregulated in neurons of the IBZ [97]. ‡

Upregulation in mSOD1 ADEV mouse model is stopped after miR-146a induction [69]. After ISCI injury, stimulates polarization of reactive neurotrophic neuroprotective astrocytes [98]. *

Repress FasL in microglia o inhibit neurotoxic hypoxia activated microglia [99]. ⁑

Diminish apoptosis modulating tumor suppressor PDC4I3K/AKT/GSK-3β, including apoptosis triggered by neurotoxic Aβ1–42 in SH-SY5Y [100]. PTEN independent oncogene [96]. ∞ ‡

Upregulates VEGF promoting angiogenesis in transformed and non-transformed non CNS tumoral cell lines [101]. ∞

miR-30b-5p

Ischemia

Upregulated in ADEV under IPC in rat [65].

Differentially upregulated in MS, associated with non-progressive forms of the disease [9]. Downregulated in ALS [102]. Elevated in PD 6- hydroxydopamine induced rat models [103]. •

Involved in diabetic retinopathy with possible biomarker applications, regulates angiogenesis [104]. ⸰

Targets SIRT1 inhibiting autophagy of the mitochondria [103].

Suppresses lysosomal biogenesis and autophagy by inhibiting TFEB targets pre-transcriptionally [105]. ∞

miR-32

HIBD

Downregulated in ADEV after HIBD in rat [68].

Involved in the maintenance of myelin fine tuning SLC45A3 and CLDN-11 expression [106]. ˟

Downregulated in glioma, targeted ABCC4 and EZH2, it reduces proliferation and migration [107]. ∞ *

Upregulated in some cancer tissues, reduces apoptosis and promotes proliferation and migration targeting OTUD3 and promoting MYC [108][109]. ∞

miR-92b-3p

Ischemia, OSA, ASCI

Upregulated in ADEV under IPC in rat [65].

Reduces inflammation after ischemic stroke. Downregulated in OSA, apnea, hypopnea [110]. Downregulated after ASCI, promotes functional recovery after ASCI [111]. •

Diminishes apoptosis, cell death, mitochondrial dysfunction and favors neurite growth [65][111], including IHR induced apoptosis. Decreases ROS production, MAOA hyperactivity and PTEN expression. Promotes phosphorylation of AKT, and GAP43 and NF-200 expression

[110][111]. ‡

Inhibits IHR-induced NF-κB1, PTGS1, TNF-α, and TGF-β expression [110]. +

Downregulated under hypoxia conditions in PASMCs, reverse proliferation and cell cycle induced under hypoxia conditions [112]. ζ

Inhibits IHR-induced apoptosis and CXCL5 and ADRB1 expression [110]. ∞, α

Regulate proliferation, apoptosis, differentiation, and metastasis[112]. ∞

mir-100

Il-1β stimulation

Upregulated in ADEV under Il-1β and ATP induction in primary rat astrocytes [63].

Downregulated in autosomal recessive NDD SMA [113][114].. ⸸

Induces apoptosis in retinal ganglion cells exposed to H2O2 [115]. ‡

Activates TLR8 receptors post-translationally causing indirect neuronal microenvironment dysregulation, activates cytokine and chemokine release [116] Downregulates in activated microglia, ameliorates motor function loss after SCI by targeting TLR4 and NF-κB [117]. ⁑

Activates cytokine and chemokine release in macrophages [116]. α

Downregulated in hypoxia induced proliferation of PASMCs, suppress mTOR expression leading to inhibition of proliferation [118]. ζ

Overexpressed in EVs from CRC cells mutant KRAS expressing [119] ∞ ο

miR-107

TNF-α stimulation

Upregulated in ADEV after TNF-α stimulation in primary rat astrocytes [63].

Involved in AD, targets BACE1, CDK5, ADAM1, increases neuronal differentiation [120]. •

Higher expression correlates with lower overall patient survival in high grade gliomas [121]

Alter key aggressiveness characteristics of prostate cancer cells such as proliferation, modulates lipid metabolism, adjacent non-tumoral tissue shows downregulation. Its expression in cancer correlates with levels in plasma [122]. ∞

mir-138

Morphine-mediated neuroinflammatory microenvironment

Upregulated in ADEV under morphine stimulated conditions in mouse [58].

Activates astrocytes induced by Tat in HAND [123]. *

Internalizes mir-138 charged ADEV. Activation of microglia through direct activation of the TLR7-NF-kB axis [58].⁑

Promotes early differentiation of oligodendrocytes [124]. ˟

Inhibits adipocyte differentiation reducing EZH2 expression [125]. μ

miR-146a

Early asymptomatic mSOD1 ALS model, ethanol activated neuroinflammation

Upregulated in ADEV after ethanol induction in mouse astrocytes [66], Identified in ADEV from ALS mSOD1 mouse model with neurodegeneration stage not specified, downregulated [69].

Involvement in pathogenesis of MS, AD, prion disease, neurotropic virus and metal sulfate induced toxicity [126] and neuroprotective in specific contexts in ALS and stroke [69][127]. •

Upregulated after stroke in NPC. Increases myelinization protein expression and differentiation towards oligodendrocyte lineage [127]. ⸸ ˟

Increases inflammation and its own expression in cortical neurons [66]. ‡

Attenuates miR-21 and miR-155 expression in ALS mSOD1 mouse model, decreases astrocyte reactivity and decreases proinflammatory miRNA associated exosomal cargo production [69]. Downregulated in ALS [128]. *

Downregulated by infection (RCV virus), it diminish TRAF-6 expression, JNK activation and lung inflammatory infiltration, reduces L-1β, IL -6 and TNF-α production [129]. e

miR-155

EAE

Neuroinflammation, proinflammatory cytokines

Identified in ADEV from ALS mSOD1 mouse model with neurodegeneration stage not specified, upregulated [69]. Downregulated in spinal cord of mice with EAE [130].

Globally upregulated in AD, related with inflammation targets CFH [120][126].. Upregulated in EAE MS mouse model [131], it expression is very high in MS lesions, favors proinflammatory conditions and negatively regulates BBB [126][130]. •

Downregulated in ADEV in ALS mSOD1 mouse model by miR-146a induction [69] *

Upregulated by proinflammatory cytokines [69]. Downregulates fatty acid metabolism associated genes [130]. +

Increases macrophage migration, mediates activation of mononuclear phagocytes, [132] α

Constitutively highly expressed [126], promotes differentiation of TH17 cells and activation of T-cells and dendritic cells [130]. δ

ROS diminish miR-155-5p expression in tumor exosomes leading to immunosuppressive tumor growth [132]. ∞

mir-182

SCI, HIBD, LPS Ethanol induced neuro-inflammation

Downregulated in ADEV after HIBD in rat [68], upregulated in ADEV after ethanol induction in mouse astrocytes [66] Downregulated in SCI of mice [133].

Anti-inflammatory miR [133]. After ischaemia exacerbates BBB dysfunction [134]. •

Enriched in neurons. Increased dendrite tree complexity, axon and neurite outgrowth, favoring expression of neurofilament-M and neurofilament-L, and AKT phosphorylation [135]. Improves SCI reducing apoptosis [133]. ⸸ ‡

Increases in ethanol-treated wild type astrocytes in a TLR4-dependent response [66]. *

Inflammatory suppressor (downregulates TNF-α, IL-6, IL-1β), apoptosis reduction by caspase-3 downregulation. Decreases expression after LPS [133]. ∞ ⁑

Targeted MTSS1 tumor suppressor transcript to inhibit proliferation and migration in glioma [136]. ∞

Inhibited apoptosis regulating PDCD4 and PACS2, under non-ischemic heart failure [137]. γ

Downregulated after Ischemia Reperfusion (I/R). It reduces autophagy stimulating mTOR and targeting Deptor, thus reducing lesion area after I/R [138]. ο

Biomarker in prostate cancer [139]. ∞

mir-200b

Ethanol induced neuro-inflammation

Upregulated in ADEV after ethanol induction in mouse astrocytes [66], downregulated in ADEV after HIBD in rat [68].

Targets APP gene downregulating amyloid beta (Aβ), however Aβ42 inhibits its expression (possibly halts AD progression) [140]. •

Increases in ethanol treated wild type astrocytes in a TLR4-dependent response [66]. *

Upregulated by Aβ, its transfection reduces Aβ secretion in conditioned media, relieve memory impairments and downregulates targets such as IRS-1pSer potentially diminishing insulin resistance [141]. ‡

Under glucotoxicity increases apoptosis of human retinal pigment epithelial cells [142]. ε

miR-873a-5p

TBI

Upregulated after TBI induction in mouse [67].

Improve neurological deficits associated with TBI, exhibiting a neuroprotective role regulating inflammatory signals [67]. Targets A20 (TNFAIP3) and targeted by HOTAIRM1 a miR-sponge associated with neuronal apoptosis [143][144]. •

Released by activated astrocytes [67]. *

Decreases ERK and NF-κB p65 phosphorylation inhibiting LPS induced M1 phenotype and inflammatory signaling, promotes microglia M2 polarization after TBI [67]. ⁑

Proapoptotic inhibitor of cell growth, downregulated in glioblastoma [145]. ∞

Target cells: ‡-Neurons, *-Astrocytes, ⁑-Microglia, ˟-Oligodendrocyte/OPCs, ⸸-Neural Progenitor/Neural Stem cell, +-Endotelial cells, •-CNS non-identified tissue, α-Monocyte/Macrophage, γ-Cardiomyocytes, δ-Limphocytes, ε-Epithelial cells, ζ- Smooth Muscle cells, μ-Preadipocyte/Adipocyte, ο-Enterocytes/Intestinal mucosa epitelial, π-Osteoblasts/Osteogenic precursor, ∞-Cancer, ⸰-non-specified peripheral origin.

References

  1. Catanesi, M.; D’Angelo, M.; Tupone, M.G.; Benedetti, E.; Giordano, A.; Castelli, V.; Cimini, A. MicroRNAs Dysregulation and Mitochondrial Dysfunction in Neurodegenerative Diseases. Int. J. Mol. Sci. 2020, 21, 5986.
  2. Feigin, V.L.; Nichols, E.; Alam, T.; Bannick, M.S.; Beghi, E.; Blake, N.; Culpepper, W.J.; Dorsey, E.R.; Elbaz, A.; Ellenbogen, R.G.; et al. Global, Regional, and National Burden of Neurological Disorders, 1990–2016: A Systematic Analysis for the Global Burden of Disease Study 2016. Lancet Neurol. 2019, 18, 459–480.
  3. Erkkinen, M.G.; Kim, M.O.; Geschwind, M.D. Clinical Neurology and Epidemiology of the Major Neurodegenerative Diseases. Cold Spring Harb. Perspect. Biol. 2018, 10, a033118.
  4. Sandor, C.; Honti, F.; Haerty, W.; Szewczyk-Krolikowski, K.; Tomlinson, P.; Evetts, S.; Millin, S.; Keane, T.; McCarthy, S.A.; Durbin, R.; et al. Whole-Exome Sequencing of 228 Patients with Sporadic Parkinson’s Disease. Sci. Rep. 2017, 7, 41188.
  5. Syeda, T.; Cannon, J.R. Environmental Exposures and the Etiopathogenesis of Alzheimer’s Disease: The Potential Role of BACE1 as a Critical Neurotoxic Target. J. Biochem. Mol. Toxicol. 2021, 35, e22694.
  6. Steenhof, M.; Stenager, E.; Nielsen, N.M.; Kyvik, K.; Möller, S.; Hertz, J.M. Familial Multiple Sclerosis Patients Have a Shorter Delay in Diagnosis than Sporadic Cases. Mult. Scler. Relat. Disord. 2019, 32, 97–102.
  7. Bloem, B.R.; Okun, M.S.; Klein, C. Parkinson’s Disease. Lancet 2021, 397, 2284–2303.
  8. Hao, N.; Wang, Z.; Liu, P.; Becker, R.; Yang, S.; Yang, K.; Pei, Z.; Zhang, P.; Xia, J.; Shen, L.; et al. Acoustofluidic Multimodal Diagnostic System for Alzheimer’s Disease. Biosens. Bioelectron. 2022, 196, 113730.
  9. Ebrahimkhani, S.; Vafaee, F.; Young, P.E.; Hur, S.S.J.; Hawke, S.; Devenney, E.; Beadnall, H.; Barnett, M.H.; Suter, C.M.; Buckland, M.E. Exosomal MicroRNA Signatures in Multiple Sclerosis Reflect Disease Status. Sci. Rep. 2017, 7, 14293.
  10. Prabhakar, P.; Retnaswami, S.; Christopher, R. Circulating MicroRNAs as Potential Biomarkers for the Identi Fi Cation of Vascular Dementia Due to Cerebral Small Vessel Disease. Age Ageing 2017, 46, 861–864.
  11. Hansson, O. Biomarkers for Neurodegenerative Diseases. Nat. Med. 2021, 27, 954–963.
  12. Brazaca, L.C.; Sampaio, I.; Zucolotto, V.; Janegitz, B.C. Applications of Biosensors in Alzheimer’s Disease Diagnosis. Talanta 2020, 210, 120644.
  13. Swarbrick, S.; Wragg, N.; Ghosh, S.; Stolzing, A. Systematic Review of MiRNA as Biomarkers in Alzheimer’s Disease. Mol. Neurobiol. 2019, 56, 6156–6167.
  14. Katsuno, M.; Sahashi, K.; Iguchi, Y.; Hashizume, A. Preclinical Progression of Neurodegenerative Diseases. Nagoya J. Med. Sci. 2018, 80, 289–298.
  15. Le, W.; Dong, J.; Li, S.; Korczyn, A.D. Can Biomarkers Help the Early Diagnosis of Parkinson’s Disease? Neurosci. Bull. 2017, 33, 535–542.
  16. Nandi, S.K.; Singh, D.; Upadhay, J.; Gupta, N.; Dhiman, N.; Mittal, S.K.; Mahindroo, N. Identification of Tear-Based Protein and Non-Protein Biomarkers: Its Application in Diagnosis of Human Diseases Using Biosensors. Int. J. Biol. Macromol. 2021, 193, 838–846.
  17. Kim, K.; Kim, M.J.; Kim, D.W.; Kim, S.Y.; Park, S.; Park, C.B. Clinically Accurate Diagnosis of Alzheimer’s Disease via Multiplexed Sensing of Core Biomarkers in Human Plasma. Nat. Commun. 2020, 11, 119.
  18. Tan, R.; Wang, Y.; Mi, X.; Li, H.; Tu, Y. A Dual-Screening Electrochemiluminescent Aptasensor Based on a Mesoporous Silica Nano-Sieve for Specific Detection of Amyloid-β Monomer. Sens. Actuators B Chem. 2022, 352 Pt 2, 131065.
  19. Bateman, R.J.; Wen, G.; Morris, J.C.; Holtzman, D.M. Fluctuations of CSF Amyloid-β Levels. Neurology 2007, 68, 666–669.
  20. Knopman, D.S.; Amieva, H.; Petersen, R.C.; Chételat, G.; Holtzman, D.M.; Hyman, B.T.; Nixon, R.A.; Jones, D.T. Alzheimer Disease. Nat. Rev. Dis. Prim. 2021, 7, 33.
  21. Souza, D.G.; Almeida, R.F.; Souza, D.O.; Zimmer, E.R. The Astrocyte Biochemistry. Semin. Cell Dev. Biol. 2019, 95, 142–150.
  22. Colangelo, A.M.; Alberghina, L.; Papa, M. Astrogliosis as a Therapeutic Target for Neurodegenerative Diseases. Neurosci. Lett. 2014, 565, 59–64.
  23. Mozafari, N.; Ashrafi, H.; Azadi, A. Targeted Drug Delivery Systems to Control Neuroinflammation in Central Nervous System Disorders. J. Drug Deliv. Sci. Technol. 2021, 66, 102802.
  24. Sofroniew, M.V. Astrogliosis. Cold Spring Harb. Perspect. Biol. 2015, 7, a020420.
  25. Kuter, K.; Olech, Ł.; Głowacka, U.; Paleczna, M. Astrocyte Support Is Important for the Compensatory Potential of the Nigrostriatal System Neurons during Early Neurodegeneration. J. Neurochem. 2019, 148, 63–79.
  26. Guo, T.; Zhang, D.; Zeng, Y.; Huang, T.Y.; Xu, H.; Zhao, Y. Molecular and Cellular Mechanisms Underlying the Pathogenesis of Alzheimer’s Disease. Mol. Neurodegener. 2020, 15, 40.
  27. Maragakis, N.J.; Rothstein, J.D. Mechanisms of Disease: Astrocytes in Neurodegenerative Disease. Nat. Clin. Pract. Neurol. 2006, 2, 679–689.
  28. Su, C.; Zhao, K.; Xia, H.; Xu, Y. Peripheral Inflammatory Biomarkers in Alzheimer’s Disease and Mild Cognitive Impairment: A Systematic Review and Meta-Analysis. Psychogeriatrics 2019, 19, 300–309.
  29. Castellani, R.J.; Lee, H.G.; Zhu, X.; Nunomura, A.; Perry, G.; Smith, M.A. Neuropathology of Alzheimer Disease: Pathognomonic but Not Pathogenic. Acta Neuropathol. 2006, 111, 503–509.
  30. Kishore, U. Neurodegenerative Diseases; BoD: Norderstedt, Germany, 2013.
  31. Carter, S.F.; Schöll, M.; Almkvist, O.; Wall, A.; Engler, H.; Långström, B.; Nordberg, A. Evidence for Astrocytosis in Prodromal Alzheimer Disease Provided by 11C-Deuterium-L-Deprenyl: A Multitracer PET Paradigm Combining 11C-Pittsburgh Compound B and 18F-FDG. J. Nucl. Med. 2012, 53, 37–46.
  32. Wilson, H.; Dervenoulas, G.; Pagano, G.; Tyacke, R.J.; Polychronis, S.; Myers, J.; Gunn, R.N.; Rabiner, E.A.; Nutt, D. Imidazoline 2 Binding Sites Reflecting Astroglia Pathology in Parkinson’s Disease: An in Vivo 11C-BU99008 PET Study. Brain 2019, 142, 3116–3128.
  33. Linnerbauer, M.; Wheeler, M.A.; Quintana, F.J. Astrocyte Crosstalk in CNS Inflammation. Neuron 2020, 108, 608.
  34. Sofroniew, M.V. Astrocyte Reactivity: Subtypes, States, and Functions in CNS Innate Immunity. Trends Immunol. 2020, 41, 758–770.
  35. Santello, M.; Toni, N.; Volterra, A. Astrocyte Function from Information Processing to Cognition and Cognitive Impairment. Nat. Neurosci. 2019, 22, 154–166.
  36. Bylicky, M.A.; Mueller, G.P.; Day, R.M. Mechanisms of Endogenous Neuroprotective Effects of Astrocytes in Brain Injury. Oxidative Med. Cell. Longev. 2018, 2018, 6501031.
  37. Xie, K.; Qin, Q.; Long, Z.; Yang, Y.; Peng, C.; Xi, C.; Li, L.; Wu, Z.; Daria, V.; Zhao, Y.; et al. High-Throughput Metabolomics for Discovering Potential Biomarkers and Identifying Metabolic Mechanisms in Aging and Alzheimer’s Disease. Front. Cell Dev. Biol. 2021, 9, 335.
  38. Patil, S.; Chan, C. Palmitic and Stearic Fatty Acids Induce Alzheimer-like Hyperphosphorylation of Tau in Primary Rat Cortical Neurons. Neurosci. Lett. 2005, 384, 288–293.
  39. Ortiz-Rodriguez, A.; Acaz-Fonseca, E.; Boya, P.; Arevalo, M.A.; Garcia-Segura, L.M. Lipotoxic Effects of Palmitic Acid on Astrocytes Are Associated with Autophagy Impairment. Mol. Neurobiol. 2018, 56, 1665–1680.
  40. González-Giraldo, Y.; Garcia-Segura, L.M.; Echeverria, V.; Barreto, G.E. Tibolone Preserves Mitochondrial Functionality and Cell Morphology in Astrocytic Cells Treated with Palmitic Acid. Mol. Neurobiol. 2017, 55, 4453–4462.
  41. González-Giraldo, Y.; Forero, D.A.; Echeverria, V.; Garcia-Segura, L.M.; Barreto, G.E. Tibolone Attenuates Inflammatory Response by Palmitic Acid and Preserves Mitochondrial Membrane Potential in Astrocytic Cells through Estrogen Receptor Beta. Mol. Cell. Endocrinol. 2019, 486, 65–78.
  42. Liu, L.; Martin, R.; Kohler, G.; Chan, C. Palmitate Induces Transcriptional Regulation of BACE1 and Presenilin by STAT3 in Neurons Mediated by Astrocytes. Exp. Neurol. 2013, 248, 482–490.
  43. Liu, L.; Martin, R.; Chan, C. Palmitate-Activated Astrocytes via Serine Palmitoyltransferase Increase BACE1 in Primary Neurons by Sphingomyelinases. Neurobiol. Aging 2013, 34, 540–550.
  44. Benzinger, T.L.S.; Blazey, T.; Jack, C.R.; Koeppe, R.A.; Su, Y.; Xiong, C.; Raichle, M.E.; Snyder, A.Z.; Ances, B.M.; Bateman, R.J.; et al. Regional Variability of Imaging Biomarkers in Autosomal Dominant Alzheimer’s Disease. Proc. Natl. Acad. Sci. USA 2013, 110, E4502–E4509.
  45. Winocur, G.; Greenwood, C.E. Studies of the Effects of High Fat Diets on Cognitive Function in a Rat Model. Neurobiol. Aging 2005, 26, 46–49.
  46. Ho, L.; Qin, W.; Pompl, P.N.; Xiang, Z.; Wang, J.; Zhao, Z.; Peng, Y.; Cambareri, G.; Rocher, A.; Mobbs, C.V.; et al. Diet-Induced Insulin Resistance Promotes Amyloidosis in a Transgenic Mouse Model of Alzheimer’s Disease. FASEB J. 2004, 18, 902–904.
  47. Goldman, S.E.; Goez, D.; Last, D.; Naor, S.; Liraz Zaltsman, S.; Sharvit-Ginon, I.; Atrakchi-Baranes, D.; Shemesh, C.; Twitto-Greenberg, R.; Tsach, S.; et al. High-Fat Diet Protects the Blood–Brain Barrier in an Alzheimer’s Disease Mouse Model. Aging Cell 2018, 17, e12818.
  48. Ghaddar, B.; Diotel, N. Zebrafish: A New Promise to Study the Impact of Metabolic Disorders on the Brain. Int. J. Mol. Sci. 2022, 23, 5372.
  49. Booth, H.D.E.; Hirst, W.D.; Wade-Martins, R. The Role of Astrocyte Dysfunction in Parkinson’s Disease Pathogenesis. Trends Neurosci. 2017, 40, 358.
  50. Deng, H.; Wang, P.; Jankovic, J. The Genetics of Parkinson Disease. Ageing Res. Rev. 2018, 42, 72–85.
  51. Chamoli, M.; Chinta, S.J.; Andersen, J.K. An Inducible MAO-B Mouse Model of Parkinson’s Disease: A Tool towards Better Understanding Basic Disease Mechanisms and Developing Novel Therapeutics. J. Neural Transm. 2018, 125, 1651–1658.
  52. Price, B.R.; Norris, C.M.; Sompol, P.; Wilcock, D.M. An Emerging Role of Astrocytes in Vascular Contributions to Cognitive Impairment and Dementia. J. Neurochem. 2018, 144, 644–650.
  53. Arba, F.; Mair, G.; Phillips, S.; Sandercock, P.; Wardlaw, J.M. Improving Clinical Detection of Acute Lacunar Stroke: Analysis From the IST-3. Stroke 2020, 51, 1411.
  54. Qu, P.; Cheng, K.; Gao, Q.; Li, Y.; Wang, M. Application Value of Serum Hcy, TLR4, and CRP in the Diagnosis of Cerebral Small Vessel Disease. Evidence-based Complement. Altern. Med. 2022, 2022, 4025965.
  55. Ponath, G.; Park, C.; Pitt, D. The Role of Astrocytes in Multiple Sclerosis. Front. Immunol. 2018, 9, 217.
  56. Mayo, L.; Trauger, S.A.; Blain, M.; Nadeau, M.; Patel, B.; Alvarez, J.I.; Mascanfroni, I.D.; Yeste, A.; Kivisäkk, P.; Kallas, K.; et al. Regulation of Astrocyte Activation by Glycolipids Drives Chronic CNS Inflammation. Nat. Med. 2014, 20, 1147–1156.
  57. Sochocka, M.; Diniz, B.S.; Leszek, J. Inflammatory Response in the CNS: Friend or Foe? Mol. Neurobiol. 2017, 54, 8071–8089.
  58. Ke, L.; Niu, F.; Hu, G.; Yang, L.; Dallon, B.; Villareal, D.; Buch, S. Morphine-Mediated Release OfmiR-138 in Astrocyte-Derived Extracellular Vesicles Promotes Microglial Activation. J Extracell. Vesicles 2020, 10, e12027.
  59. Pozo, P.H.E.; del Espinosa, P.S.; Donadi, E.A.; Martinez, E.Z.; Salazar-Uribe, J.C.; Guerrero, M.A.; Moriguti, J.C.; Colcha, M.C.; Garcia, S.E.; Naranjo, R.; et al. Cognitive Decline in Adults Aged 65 and Older in Cumbayá, Quito, Ecuador: Prevalence and Risk Factors. Cureus 2018, 10, e3269.
  60. Muscat, S.M.; Deems, N.P.; D’Angelo, H.; Kitt, M.M.; Grace, P.M.; Andersen, N.D.; Silverman, S.N.; Rice, K.C.; Watkins, L.R.; Maier, S.F.; et al. Postoperative Cognitive Dysfunction Is Made Persistent with Morphine Treatment in Aged Rats. Neurobiol. Aging 2021, 98, 214–224.
  61. Balaban, D.; Miyawaki, E.K.; Bhattacharyya, S.; Torre, M. The Phenomenon of Clasmatodendrosis. Heliyon 2021, 7, e07605.
  62. Fernandes, L.M.P.; Lopes, K.S.; Santana, L.N.S.; Fontes-Júnior, E.A.; Ribeiro, C.H.M.A.; Silva, M.C.F.; de Oliveira Paraense, R.S.; Crespo-López, M.E.; Gomes, A.R.Q.; Lima, R.R.; et al. Repeated Cycles of Binge-like Ethanol Intake in Adolescent Female Rats Induce Motor Function Impairment and Oxidative Damage in Motor Cortex and Liver, but Not in Blood. Oxidative Med. Cell. Longev. 2018, 2018, 3467531.
  63. Chaudhuri, A.D.; Dastgheyb, R.M.; Yoo, S.-W.; Trout, A.; Talbot, C.C., Jr.; Hao, H.; Witwer, K.W.; Haughey, N.J. TNF Alpha and IL-1 Beta Modify the MiRNA Cargo of Astrocyte Shed Extracellular Vesicles to Regulate Neurotrophic Signaling in Neurons. Cell Death Dis. 2018, 9, 363.
  64. Collado-Pérez, R.; García-Piqueres, J.; Jiménez-Hernaiz, M.; Argente, J.; Belsham, D.D.; Frago, L.M.; Chowen, J.A. Fatty Acids Modify the MicroRNA Content of Exosomes Released by Hypothalamic Astrocytes and the Response of POMC Neurons to These Exosomes. J. Endocr. Soc. 2021, 5 (Suppl. 1), A46.
  65. Xu, L.; Cao, H.; Xie, Y.; Zhang, Y.; Du, M.; Xu, X.; Ye, R.; Liu, X. Exosome-Shuttled MiR-92b-3p from Ischemic Preconditioned Astrocytes Protects Neurons against Oxygen and Glucose Deprivation. Brain Res. 2019, 1717, 66–73.
  66. Ibáñez, F.; Montesinos, J.; Ureña-peralta, J.R.; Guerri, C. TLR4 Participates in the Transmission of Ethanol-Induced Neuroinflammation via Astrocyte-Derived Extracellular Vesicles. J. Neuroinflamm. 2019, 16, 136.
  67. Long, X.; Yao, X.; Jiang, Q.; Yang, Y.; He, X.; Tian, W.; Zhao, K.; Zhang, H. Astrocyte-Derived Exosomes Enriched with MiR-873a-5p Inhibit Neuroinflammation via Microglia Phenotype Modulation after Traumatic Brain Injury. J. Neuroinflamm. 2020, 17, 89.
  68. Du, L.; Jiang, Y.; Sun, Y. Astrocyte-Derived Exosomes Carry MicroRNA-17-5p to Protect Neonatal Rats from Hypoxic-Ischemic Brain Damage via Inhibiting BNIP-2 Expression. Neurotoxicology 2021, 83, 28–39.
  69. Barbosa, M.; Gomes, C.; Vaz, A.R.; Brites, D. Upregulation of MiR-146a Attenuates ALS Mouse Cortical Astrocytes Reactivity and Decrease MiRNA-Inflammatory Associated Exosomal Cargo. Free Radic. Biol. Med. 2018, 120, S158.
  70. Yao, Y.; Wang, W.; Jing, L.; Wang, Y.; Li, M.; Hou, X.; Wang, J.; Peng, T.; Teng, J.; Jia, Y. Let-7f Regulates the Hypoxic Response in Cerebral Ischemia by Targeting NDRG3. Neurochem. Res. 2017, 42, 446–454.
  71. Daneshafrooz, N.; Joghataei, M.T.; Mehdizadeh, M.; Alavi, A.; Barati, M.; Panahi, B.; Teimourian, S.; Zamani, B. Identification of Let-7f and MiR-338 as Plasma-Based Biomarkers for Sporadic Amyotrophic Lateral Sclerosis Using Meta-Analysis and Empirical Validation. Sci. Rep. 2022, 12, 1373.
  72. Gámez-Valero, A.; Campdelacreu, J.; Vilas, D.; Ispierto, L.; Reñé, R.; Álvarez, R.; Armengol, M.P.; Borràs, F.E.; Beyer, K. Exploratory Study on MicroRNA Profiles from Plasma-Derived Extracellular Vesicles in Alzheimer’s Disease and Dementia with Lewy Bodies. Transl. Neurodegener. 2019, 8, 31.
  73. Huang, H.-T.; Hsien, H.H.; Wu, H.-T.; Tsai, S.-F.; Huang, H.-Y.; Kuo, Y.-M.; Chen, P.-S.; Yang, C.-S.; Tzen, S.-F. High Fat Diet Induces Mitochondria Stress and Impairs Myelin Structure in Rat Hypothalamus. Glia 2017, 65, E103–E578.
  74. Deng, Z.; Wei, Y.; Yao, Y.; Gao, S.; Wang, X. Let-7f Promotes the Differentiation of Neural Stem Cells in Rats. Am. J. Transl. Res. 2020, 12, 5752–5761.
  75. Buonfiglioli, A.; Efe, I.E.; Guneykaya, D.; Ivanov, A.; Huang, Y.; Orlowski, E.; Krüger, C.; Deisz, R.A.; Markovic, D.; Flüh, C.; et al. Let-7 MicroRNAs Regulate Microglial Function and Suppress Glioma Growth through Toll-Like Receptor 7. Cell Rep. 2019, 29, 3460–3471.e7.
  76. Yan, S.; Han, X.; Xue, H.; Zhang, P.; Guo, X.; Li, T.; Guo, X.; Yuan, G.; Deng, L.; Li, G. Let-7f Inhibits Glioma Cell Proliferation, Migration, and Invasion by Targeting Periostin. J. Cell. Biochem. 2015, 116, 1680–1692.
  77. Li, K.; Wang, Z.-Q.; Zhang, J.-L.; Lv, P.-Y. MicroRNA Let-7f Protects against H2O2-Induced Oxidative Damage in Neuroblastoma Cells by Targeting AKT-2. Arch. Med. Sci. 2020, 16, 1–10.
  78. Shibahara, Y.; Miki, Y.; Onodera, Y.; Hata, S.; Chan, M.S.M.; Yiu, C.C.P.; Loo, T.Y.; Nakamura, Y.; Akahira, J.I.; Ishida, T.; et al. Aromatase Inhibitor Treatment of Breast Cancer Cells Increases the Expression of Let-7f, a MicroRNA Targeting CYP19A1. J. Pathol. 2012, 227, 357–366.
  79. Zhao, Q.-C.; Xu, Z.-W.; Peng, Q.-M.; Zhou, J.-H.; Li, Z.-Y. Enhancement of MiR-16-5p on Spinal Cord Injury-Induced Neuron Apoptosis and Inflammatory Response through Inactivating ERK1/2 Pathway. J. Neurosurg. Sci. 2020.
  80. Sun, Y.; Xiong, Y.; Yan, C.; Chen, L.; Chen, D.; Mi, B.; Liu, G. Downregulation of MicroRNA-16-5p Accelerates Fracture Healing by Promoting Proliferation and Inhibiting Apoptosis of Osteoblasts in Patients with Traumatic Brain Injury. Am. J. Transl. Res. 2019, 11, 4746–4760.
  81. Joilin, G.; Gray, E.; Thompson, A.G.; Bobeva, Y.; Talbot, K.; Weishaupt, J.; Ludolph, A.; Malaspina, A.; Leigh, P.N.; Newbury, S.F.; et al. Identification of a Potential Non-Coding RNA Biomarker Signature for Amyotrophic Lateral Sclerosis. Brain Commun. 2020, 2, fcaa053.
  82. Wang, N.; He, L.; Yang, Y.; Li, S.; Chen, Y.; Tian, Z.; Ji, Y.; Wang, Y.; Pang, M.; Wang, Y.; et al. Integrated Analysis of Competing Endogenous RNA (CeRNA) Networks in Subacute Stage of Spinal Cord Injury. Gene 2020, 726, 144171.
  83. Tian, F.; Yang, J.; Xia, R. Exosomes Secreted from CircZFHX3-Modified Mesenchymal Stem Cells Repaired Spinal Cord Injury Through Mir-16-5p/IGF-1 in Mice. Neurochem. Res. 2022, 47, 2076–2089.
  84. You, S.; He, X.; Wang, M.; Mao, L.; Zhang, L. Tanshinone IIA Suppresses Glioma Cell Proliferation, Migration and Invasion Both In Vitro and In Vivo Partially through MiR-16-5p/Talin-1 (TLN1) Axis. Cancer Manag. Res. 2020, 12, 11309.
  85. Abyadeh, M.; Tofigh, N.; Hosseinian, S.; Hasan, M.; Amirkhani, A.; Fitzhenry, M.J.; Gupta, V.; Chitranshi, N.; Salekdeh, G.H.; Haynes, P.A.; et al. Key Genes and Biochemical Networks in Various Brain Regions Affected in Alzheimer’s Disease. Cells 2022, 11, 987.
  86. Chen, D.; Dixon, B.J.; Doycheva, D.M.; Li, B.; Zhang, Y.; Hu, Q.; He, Y.; Guo, Z.; Nowrangi, D.; Flores, J.; et al. IRE1α Inhibition Decreased TXNIP/NLRP3 Inflammasome Activation through MiR-17-5p after Neonatal Hypoxic-Ischemic Brain Injury in Rats. J. Neuroinflamm. 2018, 15, 32.
  87. Hong, P.; Jiang, M.; Li, H. Functional Requirement of Dicer1 and MiR-17-5p in Reactive Astrocyte Proliferation after Spinal Cord Injury in the Mouse. Glia 2014, 62, 2044–2060.
  88. Sajad, M.; Ahmed, M.M.; Thakur, S.C. An Integrated Bioinformatics Strategy to Elucidate the Function of Hub Genes Linked to Alzheimer’s Disease. Gene Rep. 2022, 26, 101534.
  89. Estfanous, S.; Daily, K.P.; Eltobgy, M.; Deems, N.P.; Anne, M.N.K.; Krause, K.; Badr, A.; Hamilton, K.; Carafice, C.; Hegazi, A.; et al. Elevated Expression of MiR-17 in Microglia of Alzheimer’s Disease Patients Abrogates Autophagy-Mediated Amyloid-β Degradation. Front. Immunol. 2021, 12, 2839.
  90. Hébert, S.S.; Horré, K.; Nicolaï, L.; Bergmans, B.; Papadopoulou, A.S.; Delacourte, A.; De Strooper, B. MicroRNA Regulation of Alzheimer’s Amyloid Precursor Protein Expression. Neurobiol. Dis. 2009, 33, 422–428.
  91. Chen, B.; Yang, Y.; Wu, J.; Song, J.; Lu, J. MicroRNA-17-5p Downregulation Inhibits Autophagy and Myocardial Remodelling after Myocardial Infarction by Targeting STAT3. Autoimmunity 2021, 55, 43–51.
  92. Wang, M.; Zhao, M.; Guo, Q.; Lou, J.; Wang, L. Non-Small Cell Lung Cancer Cell–Derived Exosomal MiR-17-5p Promotes Osteoclast Differentiation by Targeting PTEN. Exp. Cell Res. 2021, 408, 112834.
  93. Qin, X.; Zhu, B.; Jiang, T.; Tan, J.; Wu, Z.; Yuan, Z.; Zheng, L.; Zhao, J. MiR-17-5p Regulates Heterotopic Ossification by Targeting ANKH in Ankylosing Spondylitis. Mol. Ther. Nucleic Acids 2019, 18, 696–707.
  94. Xu, J.; Zhang, X.; Song, X.; Tang, Y. Expression of MiR-17-5p in Gastrointestinal Stromal Tumor Tissues and Its Effect on Proliferation and Apoptosis of GIST882 Cells. Chin. J. Cancer Biother. 2022, 28, 721–727.
  95. Deng, X.H.; Zhong, Y.; Gu, L.Z.; Shen, W.; Guo, J. MiR-21 Involve in ERK-Mediated Upregulation of MMP9 in the Rat Hippocampus Following Cerebral Ischemia. Brain Res. Bull. 2013, 94, 56–62.
  96. Zhou, X.; Ren, Y.; Moore, L.; Mei, M.; You, Y.; Xu, P.; Wang, B.; Wang, G.; Jia, Z.; Pu, P.; et al. Downregulation of MiR-21 Inhibits EGFR Pathway and Suppresses the Growth of Human Glioblastoma Cells Independent of PTEN Status. Lab. Investig. 2010, 90, 144–155.
  97. Buller, B.; Liu, X.; Wang, X.; Zhang, R.L.; Zhang, L.; Hozeska-Solgot, A.; Chopp, M.; Zhang, Z.G. MicroRNA-21 Protects Neurons from Ischemic Death. FEBS J. 2010, 277, 4299–4307.
  98. Su, Y.; Chen, Z.; Du, H.; Liu, R.; Wang, W.; Li, H.; Ning, B. Silencing MiR-21 Induces Polarization of Astrocytes to the A2 Phenotype and Improves the Formation of Synapses by Targeting Glypican 6 via the Signal Transducer and Activator of Transcription-3 Pathway after Acute Ischemic Spinal Cord Injury. FASEB J. 2019, 33, 10859–10871.
  99. Zhang, L.; Dong, L.Y.; Li, Y.J.; Hong, Z.; Wei, W.S. MiR-21 Represses FasL in Microglia and Protects against Microglia-Mediated Neuronal Cell Death Following Hypoxia/Ischemia. Glia 2012, 60, 1888–1895.
  100. Feng, M.G.; Liu, C.F.; Chen, L.; Feng, W.B.; Liu, M.; Hai, H.; Lu, J.M. MiR-21 Attenuates Apoptosis-Triggered by Amyloid-β via Modulating PDCD4/PI3K/AKT/GSK-3β Pathway in SH-SY5Y Cells. Biomed. Pharmacother. 2018, 101, 1003–1007.
  101. Zhao, Y.; Xu, Y.; Luo, F.; Xu, W.; Wang, B.; Pang, Y.; Zhou, J.; Wang, X.; Liu, Q. Angiogenesis, Mediated by MiR-21, Is Involved Arsenite-Induced Carcinogenesis. Toxicol. Lett. 2013, 223, 35–41.
  102. Liguori, M.; Nuzziello, N.; Introna, A.; Consiglio, A.; Licciulli, F.; D’Errico, E.; Scarafino, A.; Distaso, E.; Simone, I.L. Dysregulation of MicroRNAs and Target Genes Networks in Peripheral Blood of Patients with Sporadic Amyotrophic Lateral Sclerosis. Front. Mol. Neurosci. 2018, 11, 288.
  103. Janik, P.; Fitzgerald, J.C.; Rai, S.N.; Huo, J.; Chen, M.; Peng, L.; Gong, P.; Zheng, X.; Sun, T.; Zhang, X. Baicalein Induces Mitochondrial Autophagy to Prevent Parkinson’s Disease in Rats via MiR-30b and the SIRT1/AMPK/MTOR Pathway. Front. Neurol. 2022, 12, 646817.
  104. Mazzeo, A.; Lopatina, T.; Gai, C.; Trento, M.; Porta, M.; Beltramo, E. Functional Analysis of MiR-21-3p, MiR-30b-5p and MiR-150-5p Shuttled by Extracellular Vesicles from Diabetic Subjects Reveals Their Association with Diabetic Retinopathy. Exp. Eye Res. 2019, 184, 56–63.
  105. Guo, H.; Pu, M.; Tai, Y.; Chen, Y.; Lu, H.; Qiao, J.; Wang, G.; Chen, J.; Qi, X.; Huang, R.; et al. Nuclear MiR-30b-5p Suppresses TFEB-Mediated Lysosomal Biogenesis and Autophagy. Cell Death Differ. 2020, 28, 320–336.
  106. Shin, D.; Howng, S.Y.B.; Ptáček, L.J.; Fu, Y.H. MiR-32 and Its Target SLC45A3 Regulate the Lipid Metabolism of Oligodendrocytes and Myelin. Neuroscience 2012, 213, 29–37.
  107. Zhang, Y.; Wang, J.; An, W.; Chen, C.; Wang, W.; Zhu, C.; Chen, F.; Chen, H.; Zheng, W.; Gong, J. MiR-32 Inhibits Proliferation and Metastasis by Targeting EZH2 in Glioma. Technol. Cancer Res. Treat. 2019, 18, 1533033819854132.
  108. Jin, Y.; Cheng, H.; Cao, J.; Shen, W. MicroRNA 32 Promotes Cell Proliferation, Migration, and Suppresses Apoptosis in Colon Cancer Cells by Targeting OTU Domain Containing 3. J. Cell. Biochem. 2019, 120, 18629–18639.
  109. Scaravilli, M.; Koivukoski, S.; Gillen, A.; Bouazza, A.; Ruusuvuori, P.; Visakorpi, T.; Latonen, L. MiR-32 Promotes MYC-Driven Prostate Cancer. Oncogenesis 2022, 11, 11.
  110. Chen, Y.C.; Hsu, P.Y.; Su, M.C.; Chen, T.W.; Hsiao, C.C.; Chin, C.H.; Liou, C.W.; Wang, P.W.; Wang, T.Y.; Lin, Y.Y.; et al. Microrna Sequencing Analysis in Obstructive Sleep Apnea and Depression: Anti-Oxidant and Maoa-Inhibiting Effects of Mir-15b-5p and Mir-92b-3p through Targeting Ptgs1-Nf-Κb-Sp1 Signaling. Antioxidants 2021, 10, 1854.
  111. Chen, Z.; Li, Z.; Jiang, C.; Jiang, X.; Zhang, J. MiR-92b-3p Promotes Neurite Growth and Functional Recovery via the PTEN/AKT Pathway in Acute Spinal Cord Injury. J. Cell. Physiol. 2019, 234, 23043–23052.
  112. Hao, X.; Ma, C.; Chen, S.; Dang, J.; Cheng, X.; Zhu, D. Reverse the down Regulation of MiR-92b-3p by Hypoxia Can Suppress the Proliferation of Pulmonary Artery Smooth Muscle Cells by Targeting USP28. Biochem. Biophys. Res. Commun. 2018, 503, 3064–3077.
  113. Paul, S.; Vázquez, L.A.B.; Uribe, S.P.; Reyes-Pérez, P.R.; Sharma, A. Current Status of MicroRNA-Based Therapeutic Approaches in Neurodegenerative Disorders. Cells 2020, 9, 1698.
  114. Magri, F.; Vanoli, F.; Corti, S. MiRNA in Spinal Muscular Atrophy Pathogenesis and Therapy. J. Cell. Mol. Med. 2018, 22, 755–767.
  115. Kong, N.; Lu, X.; Li, B. Downregulation of MicroRNA-100 Protects Apoptosis and Promotes Neuronal Growth in Retinal Ganglion Cells. BMC Mol. Biol. 2014, 15, 25.
  116. Wallach, T.; Mossmann, Z.J.; Szczepek, M.; Wetzel, M.; Machado, R.; Raden, M.; Miladi, M.; Kleinau, G.; Krüger, C.; Dembny, P.; et al. MicroRNA-100-5p and MicroRNA-298-5p Released from Apoptotic Cortical Neurons Are Endogenous Toll-like Receptor 7/8 Ligands That Contribute to Neurodegeneration. Mol. Neurodegener. 2021, 16, 80.
  117. Li, X.H.; Fu, N.S.; Xing, Z.M. MiR-100 Suppresses Inflammatory Activation of Microglia and Neuronal Apoptosis Following Spinal Cord Injury via TLR4/NF-ΚB Pathway. Eur. Rev. Med. Pharmacol. Sci. 2019, 23, 8713–8720.
  118. Wang, A.P.; Li, X.H.; Gong, S.X.; Li, W.Q.; Hu, C.P.; Zhang, Z.; Li, Y.J. MIR-100 Suppresses MTOR Signaling in Hypoxia-Induced Pulmonary Hypertension in Rats. Eur. J. Pharmacol. 2015, 765, 565–573.
  119. Cha, D.J.; Franklin, J.L.; Dou, Y.; Liu, Q.; Higginbotham, J.N.; Beckler, M.D.; Weaver, A.M.; Vickers, K.; Prasad, N.; Levy, S.; et al. KRAS-Dependent Sorting of MiRNA to Exosomes. eLife 2015, 4, e07197.
  120. Sun, C.; Liu, J.; Duan, F.; Cong, L.; Qi, X. The Role of the MicroRNA Regulatory Network in Alzheimer’s Disease: A Bioinformatics Analysis. Arch. Med. Sci. 2022, 18, 206–222.
  121. Kit, O.I.; Pushkin, A.A.; Alliluyev, I.A.; Timoshkina, N.N.; Gvaldin, D.Y.; Rostorguev, E.E.; Kuznetsova, N.S. Differential Expression of MicroRNAs Targeting Genes Associated with the Development of High-Grade Gliomas. Egypt. J. Med. Hum. Genet. 2022, 23, 31.
  122. Herrero-Aguayo, V.; Sáez-Martínez, P.; Jiménez-Vacas, J.M.; Moreno-Montilla, M.T.; Montero-Hidalgo, A.J.; Pérez-Gómez, J.M.; López-Canovas, J.L.; Porcel-Pastrana, F.; Carrasco-Valiente, J.; Anglada, F.J.; et al. Dysregulation of the MiRNome Unveils a Crosstalk between Obesity and Prostate Cancer: MiR-107 Asa Personalized Diagnostic and Therapeutic Tool. Mol. Ther. Nucleic Acids 2022, 27, 1164–1178.
  123. Hu, G.; Liao, K.; Yang, L.; Pendyala, G.; Kook, Y.; Fox, H.S.; Buch, S. Tat-Mediated Induction of MiRs-34a &-138 Promotes Astrocytic Activation via Downregulation of SIRT1: Implications for Aging in HAND. J. Neuroimmune Pharmacol. 2017, 12, 420–432.
  124. Madsen, P.M.; Motti, D.; Karmally, S.; Szymkowski, D.E.; Lambertsen, K.L.; Bethea, J.R.; Brambilla, R. Oligodendroglial TNFR2 Mediates Membrane TNF-Dependent Repair in Experimental Autoimmune Encephalomyelitis by Promoting Oligodendrocyte Differentiation and Remyelination. J. Neurosci. 2016, 36, 5128–5143.
  125. Liu, Y.; Liu, H.; Li, Y.; Mao, R.; Yang, H.; Zhang, Y.; Zhang, Y.; Guo, P.; Zhan, D.; Zhang, T. Circular RNA SAMD4A Controls Adipogenesis in Obesity through the MiR-138-5p/EZH2 Axis. Theranostics 2020, 10, 4705.
  126. Devier, D.J.; Lovera, J.F.; Lukiw, W.J. Increase in NF-ΚB-Sensitive MiRNA-146a and MiRNA-155 in Multiple Sclerosis (MS) and pro-Inflammatory Neurodegeneration. Front. Mol. Neurosci. 2015, 8, 1–5.
  127. Liu, X.S.; Chopp, M.; Pan, W.L.; Wang, X.L.; Fan, B.Y.; Zhang, Y.; Kassis, H.; Zhang, R.L.; Zhang, X.M.; Zhang, Z.G. MicroRNA-146a Promotes Oligodendrogenesis in Stroke. Mol. Neurobiol. 2017, 54, 227–237.
  128. Gomes, C.; Cunha, C.; Nascimento, F.; Ribeiro, J.A.; Vaz, A.R.; Brites, D. Cortical Neurotoxic Astrocytes with Early ALS Pathology and MiR-146a Deficit Replicate Gliosis Markers of Symptomatic SOD1G93A Mouse Model. Mol. Neurobiol. 2019, 56, 2137–2158.
  129. Huang, Z.; Liu, X.; Wu, X.; Chen, M.; Yu, W. MiR-146a Alleviates Lung Injury Caused by RSV Infection in Young Rats by Targeting TRAF-6 and Regulating JNK/ERKMAPK Signaling Pathways. Sci. Rep. 2022, 12, 3481.
  130. Lopez-Ramirez, M.A.; Wu, D.; Pryce, G.; Simpson, J.E.; Reijerkerk, A.; King-Robson, J.; Kay, O.; De Vries, H.E.; Hirst, M.C.; Sharrack, B.; et al. MicroRNA-155 Negatively Affects Blood-Brain Barrier Function during Neuroinflammation. FASEB J. 2014, 28, 2551–2565.
  131. Venkatesha, S.H.; Dudics, S.; Song, Y.; Mahurkar, A.; Moudgil, K.D. The miRNA Expression Profile of Experimental Autoimmune Encephalomyelitis Reveals Novel Potential Disease Biomarkers. Int. J. Mol. Sci. 2018, 19, 3990.
  132. Li, X.; Wang, S.; Mu, W.; Barry, J.; Han, A.; Carpenter, R.L.; Jiang, B.-H.; Peiper, S.C.; Mahoney, M.G.; Aplin, A.E.; et al. Reactive Oxygen Species Reprogram Macrophages to Suppress Antitumor Immune Response through the Exosomal MiR-155-5p/PD-L1 Pathway. J. Exp. Clin. Cancer Res. 2021, 41, 41.
  133. Fei, M.; Li, Z.; Cao, Y.; Jiang, C.; Lin, H.; Chen, Z. MicroRNA-182 Improves Spinal Cord Injury in Mice by Modulating Apoptosis and the Inflammatory Response via IKKβ/NF-ΚB. Lab. Investig. 2021, 101, 1238–1253.
  134. Zhang, T.; Tian, C.; Wu, J.; Zhang, Y.; Wang, J.; Kong, Q.; Mu, L.; Sun, B.; Ai, T.; Wang, Y.; et al. MicroRNA-182 Exacerbates Blood-Brain Barrier (BBB) Disruption by Downregulating the MTOR/FOXO1 Pathway in Cerebral Ischemia. FASEB J. 2020, 34, 13762–13775.
  135. Wang, W.M.; Lu, G.; Su, X.W.; Lyu, H.; Poon, W.S. MicroRNA-182 Regulates Neurite Outgrowth Involving the PTEN/AKT Pathway. Front. Cell. Neurosci. 2017, 11, 96.
  136. Li, Z.; Zhang, L.; Liu, Z.; Huang, T.; Wang, Y.; Ma, Y.; Fang, X.; He, Y.; Zhou, Y.; Huo, L.; et al. Research Paper MiRNA-182 Regulated MTSS1 Inhibits Proliferation and Invasion in Glioma Cells. J. Cancer 2020, 11, 5840–5851.
  137. Zhou, F.; Fu, W.D.; Chen, L. MiRNA-182 Regulates the Cardiomyocyte Apoptosis in Heart Failure. Eur. Rev. Med. Pharmacol. Sci. 2019, 23, 4917–4923.
  138. Li, Y.; Luo, Y.; Li, B.; Niu, L.; Liu, J.; Duan, X. MiRNA-182/Deptor/MTOR Axis Regulates Autophagy to Reduce Intestinal Ischaemia/Reperfusion Injury. J. Cell. Mol. Med. 2020, 24, 7873–7883.
  139. Nayak, B.; Khan, N.; Garg, H.; Rustagi, Y.; Singh, P.; Seth, A.; Dinda, A.K.; Kaushal, S. Role of MiRNA-182 and MiRNA-187 as Potential Biomarkers in Prostate Cancer and Its Correlation with the Staging of Prostate Cancer. Int. Braz. J. Urol. 2020, 46, 614–623.
  140. Fu, J.; Peng, L.; Tao, T.; Chen, Y.; Li, Z.; Li, J. Regulatory Roles of the MiR-200 Family in Neurodegenerative Diseases. Biomed. Pharmacother. 2019, 119, 109409.
  141. Higaki, S.; Muramatsu, M.; Matsuda, A.; Matsumoto, K.; Satoh, J.-I.; Michikawa, M.; Niida, S. Defensive Effect of MicroRNA-200b/c against Amyloid-Beta Peptide-Induced Toxicity in Alzheimer’s Disease Models. PLoS ONE 2018, 13, e0196929.
  142. Yu, J.; Qin, M.; Li, J.; Cui, S. LncRNA SNHG4 Sponges MiR-200b to Inhibit Cell Apoptosis in Diabetic Retinopathy. Arch. Physiol. Biochem. 2021, 6, 1–6.
  143. Huang, J.; Liang, X.; Wang, J.; Kong, Y.; Zhang, Z.; Ding, Z.; Song, Z.; Guo, Q.; Zou, W. MiR-873a-5p Targets A20 to Facilitate Morphine Tolerance in Mice. Front. Neurosci. 2019, 13, 347.
  144. Fan, Y.; Li, J.; Yang, Q.; Gong, C.; Gao, H.; Mao, Z.; Yuan, X.; Zhu, S.; Xue, Z. Dysregulated Long Non-Coding RNAs in Parkinson’s Disease Contribute to the Apoptosis of Human Neuroblastoma Cells. Front. Neurosci. 2019, 13, 1320.
  145. Lin, Y.H.; Guo, L.; Yan, F.; Dou, Z.Q.; Yu, Q.; Chen, G. Long Non-Coding RNA HOTAIRM1 Promotes Proliferation and Inhibits Apoptosis of Glioma Cells by Regulating the MiR-873-5p/ZEB2 Axis. Chin. Med. J. 2020, 133, 174–182.
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