Functional analysis of mitochondrial related novel myelinating disorder gene

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K09982
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Tohoku University
• Principal Investigator: Uematsu Mitsugu 東北大学, 大学病院, 講師 (90400316)
• Co-Investigator(Kenkyū-buntansha): 植松 有里佳 (沼田) 東北大学, 大学病院, 特任助手 (70735779)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: ミトコンドリア / 髄鞘化 / 線維芽細胞 / ラット / アポトーシス / Direct reprogramming

Outline of Final Research Achievements

In this study, we analyzed the pathophysiology of the central nervous system of the novel candidate gene PNPT1, which is involved in the transport of small RNAs into mitochondria. Direct differentiation into neurons using the “Direct reprogramming” method found that in the case of myelination disorder cases with PNPT1 gene abnormality, the neurons in the cases show a decrease in survival rate that causes apoptosis earlier than in the control. Furthermore, knockdown of the PNPT1 gene in the primary culture system of dorsal root ganglia from wild-type rats confirmed that myelination was significantly delayed. Using this established experimental system, it became possible to conduct further analysis and therapeutic drug screening.

Free Research Field

小児神経学

Academic Significance and Societal Importance of the Research Achievements

低分子RNAのミトコンドリア内への輸送に関与するPNPT1遺伝子の異常による中枢神経障害の解析は、低分子RNA が先天性髄鞘化障害に関与するメカニズムを解明する鍵である。本研究により、低分子RNA がミトコンドリアへ輸送されることが髄鞘化の機序に必須であることを明らかとなり、さらに今回確立した実験系を用いて、今後治療薬のスクリーニングを行うなどの応用も可能となった。