EAAT2 Activation Regulates Glutamate Excitotoxicity and Reduces Impulsivity in a Rodent Model of Parkinson's Disease.

ABSTRACT: Parkinson's disease (PD) is a systemic disease characterized by motor and nonmotor impairments. Loss of dopaminergic neurons in the substantia nigra pars compacta region in PD disrupts dopamine-glutamate homeostasis in the corticostriatal circuit, contributing to cognitive impairment. In addition, excitatory amino acid transporter-2 (EAAT2), localized predominantly to astrocytes and responsible for > 80% of synaptic glutamate clearance, is downregulated in PD, causing glutamate spillover and excitotoxicity. This altered dopamine-glutamate homeostasis and excitotoxicity may affect reward-mediated decision-making behaviors and promote impulsive behaviors in PD. In this study, we hypothesized that GTS467, a small-molecule activator of EAAT2, could effectively reduce excitotoxicity and treat c

SUBMITTER: Das S 

PROVIDER: S-EPMC11953204 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature