Regulation of peripheral nerve function through post-translational modifications

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K07069
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurochemistry/Neuropharmacology
• Research Institution: Tokyo University of Pharmacy and Life Science
• Principal Investigator: Baba Hiroko 東京薬科大学, 薬学部, 教授 (40271499)
• Research Collaborator: Yamaguchi Yoshihide ; Otani Yoshinori ; Ohno Nobuhiko , ABiS支援者
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 末梢神経髄鞘 / シュワン細胞 / 翻訳後修飾 / P0 / 脱髄 / NEDD8 / ユビキチン

Outline of Final Research Achievements

Peripheral myelin has a role in rapid and efficient nerve conduction and its damage (demyelination) causes severe sensory or motor dysfunction. Therefore, it is important to know the molecular mechanisms of myelin formation/maintenance and demyelination. In this study, to know the role of protein modification in myelin, we made genetically modified mice. The gene encoding myelin P0 is one of the responsible genes for human peripheral neuropathy, and pathogenic involvement of protein modification has been reported. We established appropriate animal model to study role of protein modification in myelin since these P0 mutant mice show various ranges of delayed myelination, morphological abnormalities and demyelination depending on their genotypes and age.

Free Research Field

分子神経生物学

Academic Significance and Societal Importance of the Research Achievements

末梢神経髄鞘は、興奮伝導を素速く正確に行うために重要であるが、その形成や維持あるいは脱髄機序はまだ不明な点が多い。本研究では、髄鞘におけるタンパク質修飾に着目し、その解析に適した新たなマウスモデルを作製した。これらのマウスを用いることにより、髄鞘形成や形態異常、脱髄など様々な病態とタンパク質修飾との関係性を解析できるとともに、正常髄鞘の形成や維持機構の理解にも役立つ。安定した末梢髄鞘異常を示すモデルマウスは少なく、さらにP0遺伝子変異はヒトでも遺伝性末梢神経障害を生じることから、今後髄鞘の基礎研究のみでなく脱髄性疾患研究にも役立つと考えられる。