The role of astrocytic glutamate transporters GLT-1 and GLAST in neurological disorders: potential targets for neurotherapeutics.

The role of astrocytic glutamate transporters GLT-1 and GLAST in neurological disorders: potential targets for neurotherapeutics. Neuropharmacology. 2019 Mar 06;: Authors: Pajarillo E, Rizor A, Lee J, Aschner M, Lee E Abstract Glutamate is the primary excitatory neurotransmitter in the central nervous system (CNS) that initiates a rapid signal transmission in the synapse before its re-uptake into the surrounding glia, specifically astrocytes. The astrocytic glutamate transporters, glutamate-aspartate transporter (GLAST) and glutamate transporter-1 (GLT-1) and their human homologs excitatory amino acid transporter 1 (EAAT1) and 2 (EAAT2), respectively, are the major transporters that take up synaptic glutamate to maintain its optimal extracellular levels, thus preventing its accumulation in the synaptic cleft and the ensuing excitotoxicity. Growing evidence has shown that excitotoxicity is associated with various neurological disorders, including amyotrophic lateral sclerosis (ALS), Alzheimer's disease (AD), Parkinson's disease (PD), manganism, ischemia, schizophrenia, epilepsy, and autism. While the mechanisms of neurological disorders are not well understood, the dysregulation of GLAST/GLT-1 may play a significant role in excitotoxicity and associated neuropathogenesis. The expression and function of GLAST/GLT-1 may be dysregulated at the genetic, epigenetic, transcriptional or translational levels, leading to high levels of extrace...
Source: Neuropharmacology - Category: Drugs & Pharmacology Authors: Tags: Neuropharmacology Source Type: research