Summary

Neurodegeneration refers to the progressive loss of neuron structure or function, which may eventually lead to cell death. Many neurodegenerative diseases, such as amyotrophic lateral sclerosis, multiple sclerosis, Parkinson's disease, Alzheimer's disease, Huntington's disease and prion disease, are the results of neurodegenerative processes. Neurodegeneration can be found in many different levels of neuronal circuits in the brain, from molecules to systems. Since there is no known method to reverse the progressive degeneration of neurons, these diseases are considered incurable. Biomedical research has revealed many similarities between these diseases at the subcellular level, including atypical protein assembly (such as protein diseases) and induction of cell death. These similarities indicate that progress in the treatment of one neurodegenerative disease may also improve other diseases. This collection of entries aims to collect various medical research results related to neurodegeneration. We invite researchers to share their new results and ideas related to neurodegeneration.

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Entries
Topic Review
DNA Methylation in Tauopathies
Together with histone variants and modifications, alterations in nucleosome positioning, non-coding RNAs, and DNA methylation constitute the epigenetic toolkit. DNA methylation describes the chemical modification of the DNA itself by the addition of methyl groups mostly on cytosines, but also on adenines via DNA methyltransferases (DNMTs), with DNMT1 and DNMT3A being the major DNMTs in the CNS. DNA methylation effects, i.a. transcriptional control when occurring at enhancer and promoter sites, alternative promoter choice and alternative splicing. At the level of transcriptional regulation, methylated motifs of transcription factor (TF) binding sites physically impede the binding of methyl-sensitive TFs, leading to transcriptional suppression. Furthermore, the interaction of the methyl-CpG-binding domain proteins (MBDs) with methylated DNA prevents binding of TFs and promotes inactive heterochromatin formation by recruiting other chromatin and nucleosome remodeling factors.
  • 547
  • 30 Nov 2021
Topic Review
Role of Retinal Pigment Epithelium
The retinal pigment epithelium (RPE), situated upon Bruch’s membrane, plays multiple roles in the ocular system by interacting with photoreceptors and. Therefore, dysfunction of the RPE causes diseases related to vision loss, such as age-related macular degeneration (AMD). 
  • 585
  • 24 Nov 2021
Topic Review
RNA Modifications and RNA Metabolism in Neurological Disease
The intrinsic cellular heterogeneity and molecular complexity of the mammalian nervous system relies substantially on the dynamic nature and spatiotemporal patterning of gene expression. These features of gene expression are achieved in part through mechanisms involving various epigenetic processes such as DNA methylation, post-translational histone modifications, and non-coding RNA activity, amongst others. In concert, another regulatory layer by which RNA bases and sugar residues are chemically modified enhances neuronal transcriptome complexity. Similar RNA modifications in other systems collectively constitute the cellular epitranscriptome that integrates and impacts various physiological processes. The epitranscriptome is dynamic and is reshaped constantly to regulate vital processes such as development, differentiation and stress responses. Perturbations of the epitranscriptome can lead to various pathogenic conditions, including cancer, cardiovascular abnormalities and neurological diseases. These RNA modifications modulate the stability, transport and, most importantly, translation of RNA.
  • 540
  • 22 Nov 2021
Topic Review
Nanoparticle-Guided Brain Drug Delivery in Neurodegenerative Diseases
Neurodegenerative diseases (NDs) represent a heterogeneous group of aging-related disorders featured by progressive impairment of motor and/or cognitive functions, often accompanied by psychiatric disorders. NDs are denoted as ‘protein misfolding’ diseases or proteinopathies, and are classified according to their known genetic mechanisms and/or the main protein involved in disease onset and progression. 
  • 595
  • 19 Nov 2021
Topic Review
Drug Targets to Prevent Death Due to Stroke
Acute ischemic stroke (IS) is one of the most prevalent major health problems worldwide, which frequently causes severe functional disabilities and mortality. Protein-protein interaction (PPI) network analysis revealed that the backbone of the highly connective network of IS death consisted of IL6, ALB, TNF, SERPINE1, VWF, VCAM1, TGFB1, and SELE. Cluster analysis revealed immune and hemostasis subnetworks, which were strongly interconnected through the major switches ALB and VWF. Enrichment analysis revealed that the PPI immune subnetwork of death due to IS was highly associated with TLR2/4, TNF, JAK-STAT, NOD, IL10, IL13, IL4, and TGF-β1/SMAD pathways. The top biological and molecular functions and pathways enriched in the hemostasis network of death due to IS were platelet degranulation and activation, the intrinsic pathway of fibrin clot formation, the urokinase-type plasminogen activator pathway, post-translational protein phosphorylation, integrin cell-surface interactions, and the proteoglycan-integrin extracellular matrix complex (ECM). Regulation Explorer analysis of transcriptional factors shows: (a) that NFKB1, RELA and SP1 were the major regulating actors of the PPI network; and (b) hsa-mir-26-5p and hsa-16-5p were the major regulating microRNA actors. 
  • 430
  • 17 Nov 2021
Topic Review
Glutamate Protects against Catecholamine Oxidation
Catecholamines, such as dopamine and norepinephrine, take part in regulating a variety of mental processes, including cognitive ability, attention, memory, mood, and reward. Glutamate, as a neurotransmitter, plays an important role in learning, memory, neuronal plasticity, and brain development. The excessive stimulation of glutamate receptors causes the excitatory toxicity of neuron cells; thus, neurons are endowed with high-affinity glutamate transporters to enrich glutamate.
  • 684
  • 16 Nov 2021
Topic Review
Myelin Basic Protein Interaction Landscape
Intrinsically disordered myelin basic protein (MBP) is one of the key autoantigens in autoimmune neurodegeneration and multiple sclerosis particularly. MBP is highly positively charged and lacks a distinct structure in solution, and therefore its intracellular partners are still mostly enigmatic. Here authors used combination of formaldehyde-induced cross-linking followed by immunoprecipitation and liquid chromatography-tandem mass spectrometry (LC-MS/MS) to elucidate the interaction network of MBP in mammalian cells and provide the list of potential MBP interacting proteins.
  • 407
  • 15 Nov 2021
Topic Review
APOE and NF-κB in Alzheimer’s Disease
Apolipoprotein E (APOE) has three different isoforms, with APOE4 carriers representing a major risk factor for the development of Alzheimer’s disease (AD). The APOE4 isoform is associated with many pathological mechanisms, such as increased neuroinflammation. The presence of APOE4 can increase neuroinflammation via overactivation of the nuclear factor kappa B (NF-kB) pathway. The NF-kB pathway is a family of transcription factors involved with regulating over 400 genes involved with inflammation. AD is associated with sustained inflammation and an overactivation of the NF-kB pathway. Therefore, targeting the APOE4 isoform and suppressing the NF-kB pathway using anti-inflammatory compounds may result in the development of novel therapeutics for the prevention/treatment of AD.
  • 783
  • 11 Nov 2021
Topic Review
Curcumin as a Potential Neuroprotective Agent
Parkinson’s disease (PD) is a slowly progressive multisystem disorder affecting dopaminergic neurons of the substantia nigra pars compacta (SNpc), which is characterized by a decrease of dopamine (DA) in their striatal terminals. A crucial unmet demand in the management of Parkinson’s disease is the discovery of new approaches that could slow down, stop, or reverse the process of neurodegeneration. Novel potential treatments involving natural substances with neuroprotective activities are being developed. Curcumin is a polyphenolic compound isolated from the rhizomes of Curcuma longa (turmeric), and is considered a promising therapeutic and nutraceutical agent for the treatment of PD. However, molecular and cellular mechanisms that mediate the pharmacological actions of curcumin remain largely unknown. Stimulation of nicotinic receptors and, more precisely, selective α7 nicotinic acetylcholine receptors (α7-nAChR), have been found to play a major modulatory role in the immune system via the “cholinergic anti-inflammatory pathway”. Recently, α7-nAChR has been proposed to be a potential therapeutic approach in PD. In this review, the detailed mechanisms of the neuroprotective activities of curcumin as a potential therapeutic agent to help Parkinson’s patients are being discussed and elaborated on in detail.
  • 995
  • 12 Nov 2021
Topic Review
Metabolism in Retinopathy of Prematurity
Retinopathy of prematurity is defined as retinal abnormalities that occur during development as a consequence of disturbed oxygen conditions and nutrient supply after preterm birth. Both neuronal maturation and retinal vascularization are impaired, leading to the compensatory but uncontrolled retinal neovessel growth. Current therapeutic interventions target the hypoxia-induced neovessels but negatively impact retinal neurons and normal vessels. Emerging evidence suggests that metabolic disturbance is a significant and underexplored risk factor in the disease pathogenesis. Hyperglycemia and dyslipidemia correlate with the retinal neurovascular dysfunction in infants born prematurely. Nutritional and hormonal supplementation relieve metabolic stress and improve retinal maturation. Here we focus on the mechanisms through which metabolism is involved in preterm-birth-related retinal disorder from clinical and experimental investigations. We will review and discuss potential therapeutic targets through the restoration of metabolic responses to prevent disease development and progression.
  • 525
  • 09 Nov 2021
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