Host: The Japanese Pharmacological Society
Name : The 96th Annual Meeting of the Japanese Pharmacological Society
Number : 96
Location : [in Japanese]
Date : November 30, 2022 - December 03, 2022
Refractory neurological diseases may develop as a result of multiple dysfunctions of various nerves, and become more severe over time. We have proposed "reverse-translational neuroscience research", which combines human disease-specific iPS cell research and in vivo neuroscience research, to replicate cell type-specific changes in refractory neurological diseases in a particular animal disease model. The most important technique is the use of clinical samples with high-precision diagnosis and initial molecular analysis and samples with artificial genetic control. As a result, we found that a significantly increased expression of COMT in PARK2 patient-specific iPSC-derived DA neurons was associated with DNA hypomethylation. In addition, an increase in the expression of COMT was observed in DA neurons of isogenic PARK2 iPS cell lines that mimicked loss of function of PARK2 by CRISPR Cas9 technology. Finally, to produce PD model mice, overexpression of COMT in DA neurons of the substantia nigra of dopamine transporter (DAT)-Cre mice produced cataleptic behaviors associated with impaired motor coordination. This approach, which is a useful tool for applying patient information to basic research, may lead to tailor-made medications that can alleviate refractoriness.
