Glutamine antagonist JHU083 improves psychosocial behavior and sleep deficits in EcoHIV-infected mice.

ABSTRACT: Combined antiretroviral therapy ushered an era of survivable HIV infection in which people living with HIV (PLH) conduct normal life activities and enjoy measurably extended lifespans. However, despite viral control, PLH often experience a variety of cognitive, emotional, and physical phenotypes that diminish their quality of life, including cognitive impairment, depression, and sleep disruption. Recently, accumulating evidence has linked persistent CNS immune activation to the overproduction of glutamate and upregulation of glutaminase (GLS) activity, particularly in microglial cells, driving glutamatergic imbalance with neurological consequences. Our lab has developed a brain-penetrant prodrug of the glutamine antagonist 6-diazo-5-oxo-L-norleucine (DON), JHU083, that potently inhibits br

SUBMITTER: Bell BJ 

PROVIDER: S-EPMC9207540 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature