2-B-P-017 〇加藤 千聖、千葉 彩乃、野呂田 郁夫、永嶋 美華子、石井 邦明、小原 祐太郎 Kato Chisato, Ayano Chiba, Ikuo Norota, Mikako Nagashima, Kuniaki Ishii, Yutaro Obara 山形大・医・薬理学講座 Dept.Pharmacol.,Sch.Med.,Yamagata Univ. Parkinson's disease (PD) is the second most common neurodegenerative disease. It is generally understood that loss of dopaminergic neurons in substantia nigra projecting to striatum results in motor impairments. Although more than twenty causal genes have been identified to date, the 90% of patients with PD are sporadic, and pathophysiological mechanism of PD remains unclear. We previously identified a novel genetic factor, Midnolin (MIDN), for PD in Yamagata and British cohort studies. Here, we attempted to clarify the physiological role of Midn in PC12 cells. First, two monoclonal cell lines were created where frame-shift mutations were introduced in Midn by CRISPR/Cas9 method (+1/+1 insertion and -1/-1 deletion). Whereas wildtype PC12 cells promotes neurite outgrowth in response to NGF, the effect was completely blocked in both of Midn mutant PC12 cells, suggesting that Midn is essential for neurite outgrowth in PC12 cells. Neurofilament is often regarded as an index of neuronal differentiation. We therefore measured both the promoter activity and protein levels of neurofilament light chain (NF-L). NGF increased the activity of NF-L promoter and upregulated NF-L protein in wildtype PC12 cells, which was largely inhibited in Midn mutant PC12 cells. These results suggest that MIDN dysfunction may trigger the pathogenesis of PD.