The involvement of N-methyl-D-aspartate receptor (NMDAR) subunit NR1 in the pathophysiology of schizophrenia

Abstract

Schizophrenia is a severe mental illness that afflicts nearly 1% of the world population. Although the exact pathophysiology of schizophrenia is unknown, the N-methyl-d-aspartate receptor (NMDAR), a major glutamate receptor subtype, has received great attention. The NR1 subunit is often considered indispensable for functional NMDAR assemblies, abnormal modulation of which is found in patients with schizophrenia. In this review, we discuss how disrupted function of NR1 subunits in NMDAR leads to the progression and development of symptoms of schizophrenia-like behaviors in a variety of genetically modified mouse models. We also discuss some of the susceptible genes and shared signaling pathways among the schizophrenia, and how their mutations lead to NR1 subunits hypofunction. Finally, we suggest that the subunit-selective modulators of NR1 subunits in NMDA receptors may be promising tools for the therapy of schizophrenia.

Keywords: NMDA receptor; NR1 subunit; schizophrenia.

Figure 1.

Schizophrenia-susceptible genes related to the hypofunction of NR1 subunits in NMDAR represents positive function, represents negative function, and represents interaction.