Activation of glutamine synthetase (GS) as a new strategy for the treatment of major depressive disorder and other GS-related diseases.

ABSTRACT: Glutamine synthetase (GS) plays a crucial role in the homeostasis of the glutamate-glutamine cycle in the brain. Hypoactive GS causes depressive behaviors. Under chronic stress, GS has no change in expression, but its activity is decreased due to nitration of tyrosine (Tyr). Thus, we speculate that agents that prevent nitration or facilitate denitration of GS would be candidates for new antidepressants. Using human recombinant GS and mouse lysate from the medial prefrontal cortex, we demonstrated that Tyr (0.0313-0.5 µM) dose-dependently protected GS activity against peroxynitrite-induced Tyr-nitration of GS. Diet supplementation with Tyr exerted significant antidepressant effects in a chronic immobilization stress depression mouse model. We further found that dipeptides, such as tyrosyl-g

SUBMITTER: Kang JS 

PROVIDER: S-EPMC11950325 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature