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Topic Review
Role of Immune Response in Hereditary Transthyretin Amyloidosis
Hereditary transthyretin (ATTRv) amyloidosis with polyneuropathy, also known as familial amyloid polyneuropathy (FAP), represents a progressive, heterogeneous, severe, and multisystemic disease caused by pathogenic variants in the TTR gene. This autosomal-dominant neurogenetic disorder has an adult onset with variable penetrance and an inconstant phenotype, even among subjects carrying the same mutation. Historically, ATTRv amyloidosis has been viewed as a non-inflammatory disease, mainly due to the absence of any mononuclear cell infiltration in ex vivo tissues; nevertheless, a role of inflammation in its pathogenesis has been highlighted. The immune response may be involved in the development and progression of the disease. Fibrillary TTR species bind to the receptor for advanced glycation end products (RAGE), probably activating the nuclear factor κB (NF-κB) pathway. Moreover, peripheral blood levels of several cytokines, including interferon (IFN)-gamma, IFN-alpha, IL-6, IL-7, and IL-33, are altered in the course of the disease.
  • 744
  • 19 Oct 2023
Topic Review
Neurodegenerative Disorders Characterized by Mitochondrial Involvement
Neurodegenerative diseases comprise a wide spectrum of pathologies characterized by progressive loss of neuronal functions and structures. Despite having different genetic backgrounds and etiology, many studies have highlighted a point of convergence in the mechanisms leading to neurodegeneration: mitochondrial dysfunction and oxidative stress have been observed in different pathologies, and their detrimental effects on neurons contribute to the exacerbation of the pathological phenotype at various degrees.
  • 744
  • 08 Mar 2023
Topic Review
Precision Medicine of Pituitary Adenomas
Pituitary adenomas is a type of brain tumor with diverse behaviors and complexities. About half of pituitary adenomas are known to secrete specific hormones, most frequently prolactin, growth hormone, or adrenocorticotropic hormone. Despite being histologically benign, these tumors can cause significant endocrine disturbances, leading to considerable morbidity and potentially shortening lifespan. Due to their pathophysiological endocrine secretion and proximity to critical neural and vascular structures, hormone-secreting pituitary adenomas require comprehensive management.
  • 743
  • 28 Dec 2023
Topic Review
Obesity and Dementia
Obesity is a growing worldwide health problem, affecting many people due to excessive saturated fat consumption, lack of exercise, or a sedentary lifestyle. Leptin is an adipokine secreted by adipose tissue that increases in obesity and has central actions not only at the hypothalamic level but also in other regions and nuclei of the central nervous system (CNS) such as the cerebral cortex and hippocampus.
  • 741
  • 19 May 2022
Topic Review
Astrocytic Glutamatergic Transmission in Neurodegenerative Disorders
Several neurodegenerative disorders involve impaired neurotransmission, and glutamatergic neurotransmission sets a prototypical example. Glutamate is a predominant excitatory neurotransmitter where the astrocytes play a pivotal role in maintaining the extracellular levels through release and uptake mechanisms. Astrocytes modulate calcium-mediated excitability and release several neurotransmitters and neuromodulators, including glutamate, and significantly modulate neurotransmission. Accumulating evidence supports the concept of excitotoxicity caused by astrocytic glutamatergic release in pathological conditions.
  • 740
  • 27 Apr 2022
Topic Review
Relationship between EEG Abnormalities and the ASD Phenotype
The comorbidity between Autism Spectrum Disorder (ASD) and epilepsy has been widely demonstrated, and many hypotheses regarding the common neurobiological bases of these disorders have been put forward. A variable, but significant, prevalence of abnormalities on electroencephalogram (EEG) has been documented in non-epileptic children with ASD; therefore, several scientific studies have tried to demonstrate the role of these abnormalities as a possible biomarker of altered neural connectivity in ASD individuals.
  • 740
  • 23 Jan 2024
Topic Review
Patatin-like Phospholipase Domain-Containing Protein 6
Patatin-like phospholipase domain-containing protein 6 (PNPLA6), originally called Neuropathy Target Esterase (NTE), belongs to a family of hydrolases with at least eight members in mammals. PNPLA6/NTE was first identified as a key factor in Organophosphate-induced delayed neuropathy, a degenerative syndrome that occurs after exposure to organophosphates found in pesticides and nerve agents. More recently, mutations in PNPLA6/NTE have been linked with a number of inherited diseases with diverse clinical symptoms that include spastic paraplegia, ataxia, and chorioretinal dystrophy. A conditional knockout of PNPLA6/NTE in the mouse brain results in age-related neurodegeneration, whereas a complete knockout causes lethality during embryogenesis due to defects in the development of the placenta. PNPLA6/NTE is an evolutionarily conserved protein that in Drosophila is called Swiss-Cheese (SWS). Loss of SWS in the fly also leads to locomotory defects and neuronal degeneration that progressively worsen with age. 
  • 738
  • 01 Apr 2022
Topic Review
Pathogenesis and Therapeutics for Huntington’s Disease
Huntington’s disease (HD) is a debilitating neurodegenerative genetic disorder caused by an expanded polyglutamine-coding (CAG) trinucleotide repeat in the huntingtin (HTT) gene. HD behaves as a highly penetrant dominant disorder likely acting through a toxic gain of function by the mutant huntingtin protein. Widespread cellular degeneration of the medium spiny neurons of the caudate nucleus and putamen are responsible for the onset of symptomology that encompasses motor, cognitive, and behavioural abnormalities. 
  • 738
  • 06 Sep 2023
Topic Review
T Cell Chemotaxis and Infiltration in Glioblastoma
Glioblastoma is an immunologically ‘cold’ tumor, which are characterized by absent or minimal numbers of tumor-infiltrating lymphocytes (TILs). For those tumors that have been invaded by lymphocytes, they are profoundly exhausted and ineffective. While many immunotherapy approaches seek to reinvigorate immune cells at the tumor, this requires TILs to be present. 
  • 737
  • 04 Nov 2021
Topic Review
LncRNAs Display Circadian Rhythmicity in Zebrafish Larvae
Long noncoding RNAs (lncRNAs) have been shown to play crucial roles in various life processes, including circadian rhythms. Although next generation sequencing technologies have facilitated faster profiling of lncRNAs, the resulting datasets require sophisticated computational analyses. In particular, the regulatory roles of lncRNAs in circadian clocks are far from being completely understood.
  • 737
  • 07 Dec 2021
Topic Review
Pathogenesis in Multiple Sclerosis and B Cell Depletion
Multiple sclerosis (MS) is an inflammatory demyelinating autoimmune disease of the central nervous system (CNS) that typically manifests with episodes of new/recurrent neurological symptoms (i.e., relapses) followed by either complete remission or residual disability (relapsing–remitting, RR, course). Recent evidence of effectiveness of B cell-depleting monoclonal antibodies (mAbs) in MS prompted a partial revisitation of the pathogenetic paradigm of the disease, which has been, so far, considered a T cell-mediated autoimmune disorder. Although mechanisms underlying the efficacy of B cell-depleting mAbs in MS are not fully elucidated, they likely involve the impairment of pleiotropic B cell functions different from antibody secretion, such as their role as antigen-presenting cells. A potential impact of B cell-depleting mAbs on inflammation compartmentalized within the central nervous system was also suggested, but little is known about the mechanism underlying this latter phenomenon. 
  • 737
  • 15 Aug 2022
Topic Review
Role of Intestinal Microbiota in Major Depression
A major depressive disorder is a serious mental illness characterized by a pervasive low mood that negatively concerns personal life, work life, or education, affecting millions of people worldwide. Due to the complexity of the disease, the most common and effective treatments consist of a multi-therapy approach, including psychological, social, and pharmacological support with antidepressant drugs. Evidence has underlined the pivotal role of gut microbiota (GM) also in the regulation of their pharmacokinetics/pharmacodynamics, through indirect or direct mechanisms. 
  • 736
  • 27 Feb 2023
Topic Review
Pathophysiological Responses of Astrocytes to Traumatic Brain Injury
Traumatic brain injury (TBI) is an intracranial injury caused by accidents, falls, or sports. The production of endothelins (ETs) is increased in the injured brain. ET receptors are classified into distinct types, including ETA receptor (ETA-R) and ETB receptor (ETB-R). ETB-R is highly expressed in reactive astrocytes and upregulated by TBI. Activation of astrocytic ETB-R promotes conversion to reactive astrocytes and the production of astrocyte-derived bioactive factors, including vascular permeability regulators and cytokines, which cause blood–brain barrier (BBB) disruption, brain edema, and neuroinflammation in the acute phase of TBI. ETB-R antagonists alleviate BBB disruption and brain edema in animal models of TBI. The activation of astrocytic ETB receptors also enhances the production of various neurotrophic factors. These astrocyte-derived neurotrophic factors promote the repair of the damaged nervous system in the recovery phase of patients with TBI. 
  • 736
  • 09 Mar 2023
Topic Review
Ketamine plus Alcohol
Drug abuse has become a public health concern. The misuse of ketamine, a psychedelic substance, has increased worldwide. In addition, the co-abuse with alcohol is frequently identified among misusers.
  • 735
  • 01 Aug 2022
Topic Review
Serotonergic Hallucinogens in Depression Treatment
Depressive disorder is a demanding and common condition affecting more than 264 million people worldwide [1]. Despite many studies, the etiology of this disease remains unknown [2]. Some psychedelics, especially psilocybin, demonstrated an ability to reduce depressive symptoms as measured by several psychological scales, which was often sustained for months after the last psychedelic session.
  • 733
  • 26 Aug 2021
Topic Review
Cancer-Related Stroke Management
The underlying aetiopathophysiology of cancer-related strokes and thromboembolisms differs from that of noncancer-related strokes, which makes treating cancer-related strokes and thromboembolisms a distinct clinical challenge. This necessitates the development of novel, individualised diagnostic and treatment strategies.
  • 732
  • 06 May 2023
Topic Review
Clinical Evidence of Cannabinoids in Migraine
The endocannabinoid system (ECS) influences many biological functions, and hence, its pharmacological modulation may be useful for several disorders, such as migraine. Preclinical studies have demonstrated that the ECS is involved in the modulation of trigeminal excitability. Additionally, clinical data have suggested that an endocannabinoid deficiency is associated with migraine. Given these data, phytocannabinoids, as well as synthetic cannabinoids, have been tried as migraine treatments.
  • 731
  • 24 Mar 2022
Topic Review
P2X7 Receptors in Astrocytes
P2X7 receptors (P2X7Rs) in astrocytes play essential roles in PC. Although P2X7Rs trigger inflammatory and toxic responses, PC-induced P2X7Rs in astrocytes function as a switch to protect the brain against ischemia. 
  • 730
  • 21 Jun 2022
Topic Review
Central and Peripheral Nervous System Complications in AFD
Fabry disease (FD) is a recessive monogenic disease linked to chromosome X due to more than two hundred mutations in the alfa-galactosidase A (GLA) gene. In Anderson–Fabry disease (AFD), deficiency of the enzyme alfa-galactosidase A (α-GalA) leads to an abnormal buildup of globotriaosylceramide (Gb3), which is associated with end-organ damage, progressive organ failure, and subsequent clinical manifestations.
  • 730
  • 25 Jan 2024
Topic Review
Alzheimer’s Disease Genetic Susceptibility
Alzheimer’s disease (AD) is the most common form of dementia that affects millions of individuals worldwide. Although the research over the last decades has provided new insight into AD pathophysiology, there is currently no cure for the disease. AD is often only diagnosed once the symptoms have become prominent, particularly in the late-onset (sporadic) form of AD. Consequently, it is essential to further new avenues for early diagnosis. With advances in genomic analysis and a lower cost of use, the exploration of genetic markers alongside RNA molecules can offer a key avenue for early diagnosis.
  • 729
  • 14 Sep 2023
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