Roles of P bodies and stress granules in the pathogenesis of intranuclear inclusion body disease

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K07088
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Nerve anatomy/Neuropathology
• Research Institution: Hirosaki University
• Principal Investigator: Mori Fumiaki 弘前大学, 医学研究科, 准教授 (60200383)
• Co-Investigator(Kenkyū-buntansha): 三木 康生 弘前大学, 医学研究科, 助教 (30709142) ; 若林 孝一 弘前大学, 医学研究科, 教授 (50240768)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 核内封入体病 / DIS3L2 / XRN1 / エキソリボヌクレアーゼ / ポリグルタミン病

Outline of Final Research Achievements

mRNA turnover controls gene expression under various conditions in aging and neurodegenerative diseases. Polyglutamine (polyQ) diseases and intranuclear inclusion body disease (INIBD) are neurodegenerative diseases characterized by the formation of nuclear inclusions. Using immunohistochemistry with antibodies against DIS3L2 and XRN1, we examined the brains of patients with polyQ diseases and INIBD and normal control subjects. In controls, immunoreactivity for DIS3L2 and XRN1 was found in the neuronal cytoplasm and neuropil, respectively. In INIBD, immunoreactivity for DIS3L2 and XRN1 was present in neuronal and glial nuclear inclusions. Co-localization of ubiquitin and DIS3L2 or XRN1 was demonstrated in these inclusions. In polyQ diseases, however, nuclear inclusions were immunonegative for DIS3L2 and XRN1. These findings suggest that sequestration of exoribonucleases to nuclear inclusions may be related to the pathogenesis of INIBD.

Free Research Field

神経病理学

Academic Significance and Societal Importance of the Research Achievements

核内封入体病において、さまざまなストレスが、PB小体/ストレス顆粒関連蛋白の発現変動を惹起し、神経細胞ならびにアストログリアの核内にPB/SG関連蛋白が取り込まれ、核内封入体が形成される。特に成人型核内封入体病では、アストロサイトでの核内封入体形成が高頻度に起こることから、アストロサイトによる神経細胞ならびに軸索への栄養供給ならびに保護作用が阻害される可能性が考えられる。本研究で検討するPB小体/ストレス顆粒関連蛋白の動態は核内封入体病の病理発生機序の解明に役立ち、PB小体/ストレス顆粒関連蛋白の制御が神経難病治療に役立つ可能性を提示した。