International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(9), P. 4331 - 4331
Published: May 2, 2025
Schizophrenia is a complex neuropsychiatric disorder composed of primary cluster-positive symptoms, negative disorganization, neurocognitive deficits, and social cognitive impairments. While traditional antipsychotics primarily target dopamine pathways, they provide limited efficacy against deficits symptoms. Growing evidence implicates glutamatergic dysregulation, particularly N-methyl-D-aspartate receptor (NMDA-R) hypofunction, in the pathophysiology schizophrenia, making glutamate modulation promising therapeutic approach. This review explores emerging glutamate-based treatment strategies, including NMDA modulators, metabotropic (mGluR) agents, transporter regulators, kynurenine pathway inhibitors. We summarize preclinical clinical findings on co-agonists (D-serine glycine), glycine inhibitors, D-amino acid oxidase mGluR-targeted therapies, highlighting their mechanisms, efficacy, limitations. In addition, we discuss novel interventions aimed at restoring homeostasis, neuroinflammatory synaptic plasticity enhancers. Despite results, many glutamate-targeting therapies have yielded inconsistent outcomes, underscoring need for biomarker-driven patient selection optimized protocols. propose that integrating modulators with existing antipsychotic regimens may enhance response while minimizing side effects. Future research should focus refining interventions, identifying predictive biomarkers, addressing heterogeneity schizophrenia pathology. With continued advancements, has potential to transform treatment, symptoms remain largely unaddressed by current therapies.
Language: Английский