Epigenetic Regulation of Excitatory Amino Acid Transporter 2 in Neurological Disorders

Excitatory amino acid transporter 2 (EAAT2) is the predominant astrocyte glutamate transporter involved in the reuptake of the majority of the synaptic glutamate in the mammalian central nervous system (CNS). Gene expression can be altered without changing DNA sequences through epigenetic mechanisms. Mechanisms of epigenetic regulation, include DNA methylation, post-translational modifications of histones, chromatin remodeling, and small non-coding RNAs. This review is focused on neurological disorders, such as glioblastoma multiforme (GBM), Alzheimer’s disease (AD), amyotrophic lateral sclerosis (ALS), Parkinson’s disease (PD), bipolar disorder (BD), and neuroHIV where there is evidence that epigenetics plays a role in the reduction of EAAT2 expression. The emerging field of pharmaco-epigenetics provides a novel avenue for epigenetics-based drug therapy. This review highlights findings on the role of epigenetics in the regulation of EAAT2 in different neurological disorders and discusses the current pharmacological approaches used and the potential use of novel therapeutic approaches to induce EAAT2 expression in neurological disorders using CRISPR/Cas9 technology.
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research

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Source: Frontiers in Psychiatry - Category: Psychiatry Source Type: research
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Source: Frontiers in Genetics - Category: Genetics & Stem Cells Source Type: research
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Source: Frontiers in Psychiatry - Category: Psychiatry Source Type: research
Conclusion and Perspectives Since their cloning 20 years ago, the physiological importance of TREK-1 channels has continued to grow (Figure 3). Today, TREK-1 channels have been shown to be important and their presence is essential in a number of physiopathological processes. Their involvement in these different processes demonstrate the necessity to design pharmacological modulators, activators or inhibitors, of these channels to correct any TREK-1-related dysfunctions. Despites a number of studies and many molecule screenings, only few putative new drugs were identified. The activators belonging to the ML and BL series ...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
This study defines a new clinically relevant concept of T-cell senescence-mediated inflammatory responses in the pathophysiology of abnormal glucose homeostasis. We also found that T-cell senescence is associated with systemic inflammation and alters hepatic glucose homeostasis. The rational modulation of T-cell senescence would be a promising avenue for the treatment or prevention of diabetes. Intron Retention via Alternative Splicing as a Signature of Aging https://www.fightaging.org/archives/2019/03/intron-retention-via-alternative-splicing-as-a-signature-of-aging/ In recent years researchers have inv...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
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Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
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Source: Biological Psychiatry - Category: Psychiatry Authors: Tags: Review Source Type: research
Peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1 alpha) is a protein that regulates metabolism and inflammation by activating nuclear receptors, especially the family of peroxisome proliferator-activated receptors (PPARs). PGC-1 alpha and PPARs also regulate mitochondrial biogenesis, cellular energy production, thermogenesis, and lipid metabolism. Brain energy metabolism may also be regulated in part by the interaction between PGC-1 alpha and PPARs. Because neurodegenerative diseases (Huntington ’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis) and bipolar disorder h...
Source: Biological Psychiatry - Category: Psychiatry Authors: Tags: Review Source Type: research
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Source: Innovations in Clinical Neuroscience - Category: Neuroscience Authors: Tags: Assessment Tools biomarkers Cognition Current Issue Drug Development General Genetics Medical Issues Neurology Patient Assessment Psychopharmacology Scales Special Issues Supplements Trial Methodology clinical trials CNS Su Source Type: research
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Source: Clinical Prostate Cancer - Category: Cancer & Oncology Authors: Tags: Clin Transl Med Source Type: research
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