NMDA Receptors in Neurodevelopmental Disorders: Pathophysiology and Disease Models

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2024 Nov 27

PMID 39596430

Authors

Roshan Tumdam

Yara Hussein

Tali Garin-Shkolnik

Shani Stern

Affiliations

Soon will be listed here.

Abstract

N-methyl-D-aspartate receptors (NMDARs) are critical components of the mammalian central nervous system, involved in synaptic transmission, plasticity, and neurodevelopment. This review focuses on the structural and functional characteristics of NMDARs, with a particular emphasis on the GRIN2 subunits (GluN2A-D). The diversity of GRIN2 subunits, driven by alternative splicing and genetic variants, significantly impacts receptor function, synaptic localization, and disease manifestation. The temporal and spatial expression of these subunits is essential for typical neural development, with each subunit supporting distinct phases of synaptic formation and plasticity. Disruptions in their developmental regulation are linked to neurodevelopmental disorders, underscoring the importance of understanding these dynamics in NDD pathophysiology. We explore the physiological properties and developmental regulation of these subunits, highlighting their roles in the pathophysiology of various NDDs, including ASD, epilepsy, and schizophrenia. By reviewing current knowledge and experimental models, including mouse models and human-induced pluripotent stem cells (hiPSCs), this article aims to elucidate different approaches through which the intricacies of NMDAR dysfunction in NDDs are currently being explored. The comprehensive understanding of NMDAR subunit composition and their mutations provides a foundation for developing targeted therapeutic strategies to address these complex disorders.

Citing Articles

Disclosing the Complexities of Childhood Neurodevelopmental Disorders.

Tarani L, Fiore M Children (Basel). 2025; 12(1).

PMID: 39857847 PMC: 11763363. DOI: 10.3390/children12010016.

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