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Genetic insights and neurobiological implications from NRXN1 in neuropsychiatric disorders

Abstract

Many neuropsychiatric and neurodevelopmental disorders commonly share genetic risk factors. To date, the mechanisms driving the pathogenesis of these disorders, particularly how genetic variations affect the function of risk genes and contribute to disease symptoms, remain largely unknown. Neurexins are a family of synaptic adhesion molecules, which play important roles in the formation and establishment of synaptic structure, as well as maintenance of synaptic function. Accumulating genomic findings reveal that genetic variations within genes encoding neurexins are associated with a variety of psychiatric conditions such as schizophrenia, autism spectrum disorder, and some developmental abnormalities. In this review, we focus on NRXN1, one of the most compelling psychiatric risk genes of the neurexin family. We performed a comprehensive survey and analysis of current genetic and molecular data including both common and rare alleles within NRXN1 associated with psychiatric illnesses, thus providing insights into the genetic risk conferred by NRXN1. We also summarized the neurobiological evidences, supporting the function of NRXN1 and its protein products in synaptic formation, organization, transmission and plasticity, as well as disease-relevant behaviors, and assessed the mechanistic link between the mutations of NRXN1 and synaptic and behavioral pathology in neuropsychiatric disorders.

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Acknowledgements

This work was supported by grants from the Strategic Priority Research Program of the Chinese Academy of Sciences (XDB13000000 to M.L.); National Natural Science Foundation of China (81722019 to M.L., 31872778 to Z.H., and 31701133 to X.X.). Ming Li was supported by CAS Pioneer Hundred Talents Program and the 1000 Young Talents Program. Zhonghua Hu was supported by Xiangya Hospital Start-up Research Grants and Hunan 100 Talents Program.

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Hu, Z., Xiao, X., Zhang, Z. et al. Genetic insights and neurobiological implications from NRXN1 in neuropsychiatric disorders. Mol Psychiatry 24, 1400–1414 (2019). https://doi.org/10.1038/s41380-019-0438-9

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