The Role of D-Serine and D-Aspartate in the Pathogenesis and Therapy of Treatment-Resistant Schizophrenia
Р. Ф. Насырова, Aiperi K. Khasanova, Кuanysh Altynbekov, Azat R. Asadullin, Ekaterina A. Markina, Arseny Gayduk, German A. Shipulin, М. М. Петрова, N. А. Shnayder
Abstract
Schizophrenia (Sch) is a severe and widespread mental disorder. Antipsychotics (APs) of the first and new generations as the first-line treatment of Sch are not effective in about a third of cases and are also unable to treat negative symptoms and cognitive deficits of schizophrenics. This explains the search for new therapeutic strategies for a disease-modifying therapy for treatment-resistant Sch (TRS). Biological compounds are of great interest to researchers and clinicians, among which D-Serine (D-Ser) and D-Aspartate (D-Asp) are among the promising ones. The Sch glutamate theory suggests that neurotransmission dysfunction caused by glutamate N-methyl-D-aspartate receptors (NMDARs) may represent a primary deficiency in this mental disorder and play an important role in the development of TRS. D-Ser and D-Asp are direct NMDAR agonists and may be involved in modulating the functional activity of dopaminergic neurons. This narrative review demonstrates both the biological role of D-Ser and D-Asp in the normal functioning of the central nervous system (CNS) and in the pathogenesis of Sch and TRS. Particular attention is paid to D-Ser and D-Asp as promising components of a nutritive disease-modifying therapy for TRS.