Novel EAAT2 activators improve motor and cognitive impairment in a transgenic model of Huntington's disease.

ABSTRACT:

Introduction

Glutamate excitotoxicity is causal in striatal neurodegeneration underlying motor dysfunction and cognitive deficits in Huntington's disease (HD). Excitatory amino acid transporter 2 (EAAT2), the predominant glutamate transporter accounting for >90% of glutamate transport, plays a key role in preventing excitotoxicity by clearing excess glutamate from the intrasynaptic cleft. Accordingly, EAAT2 has emerged as a promising therapeutic target for prevention of neuronal excitotoxicity underlying HD and other neurodegenerative diseases.

Methods

We have previously designed novel EAAT2 positive allosteric modulator GT951, GTS467, and GTS551, with low nanomolar efficacy in glutamate uptake and favorable pharmacokinetic properties. In this study, we test the neuroprotect

SUBMITTER: Bhatnagar A 

PROVIDER: S-EPMC10282606 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature