Nagoya University Researchers Suggest Rho Kinase As A Therapeutic Target

Tokai National University Organization Nagoya University Graduate School of Medicine Graduate School of Medical Pharmacy Rinako Tanaka, Liao Jingzhu (currently a postdoctoral researcher at the University of California, Riverside), Kazuhiro Haneda (currently a lecturer at Aichi Gakuin University), Professor Kiyofumi Yamada A research group led by Project Professor Norio Ozaki of the University of Tokyo Graduate School of Medicine, Department of Psychiatric Pathology, has found that an Arhgap10 *1 gene variant *2 , which was confirmed in Japanese patients with schizophrenia based on the results of research using mice, is caused by schizophrenia . We clarified the possibility that Rho kinase *5 is involved in abnormal spine *4 density and increased sensitivity to stimulants in the medial prefrontal cortex *3 . Recently, this research group identified an ARHGAP10 gene variant strongly involved in the onset of schizophrenia through genomic analysis of Japanese patients with schizophrenia . Furthermore, as a result of generating and analyzing Arhgap10 gene-modified mice mimicking this variant, abnormal activation of Rho kinase, a downstream molecule of ARHGAP10, and decreased spine density of neurons in the medial prefrontal cortex seen in patients with schizophrenia. reported a decline in cognitive function with low-dose stimulants that had no effect on type 1 mice (Sekiguchi M et al., Transl Psychiatry, 2020; Hada K et al., Mol Brain, 2021 ). However, the association between aberrant activation of Rho kinase and these phenotypes was unknown. In this paper,

Using Arhgap10 gene-modified mice, we explored the role of Rho kinase in the pathogenesis of Arhgap10 gene variant-based schizophrenia. Administration of a Rho kinase inhibitor ameliorated abnormal spine density and increased sensitivity to stimulants in the medial prefrontal cortex of Arhgap10 gene-modified mice.
These results indicate for the first time in the world that Rho kinase can be a potential therapeutic target for schizophrenia caused by the Arhgap10 gene variant, and will greatly contribute to the development of therapeutic agents for patients with the ARHGAP10 gene variant. is expected.



The results of this research will be published in the January 2023 issue of Pharmacological Research.
This research was conducted by the Japan Agency for Medical Research and Development (AMED) Brain Science Research Strategy Promotion Program (Psychiatric and Neurological Disorder Mechanism Elucidation Project). Elucidation”).