Pathogenesis of tauopathies in terms of protein quality control mechanism

2014 Fiscal Year Final Research Report

• Project/Area Number: 24591709
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Psychiatric science
• Research Institution: Osaka University
• Principal Investigator: KUDO Takashi 大阪大学, 学内共同利用施設等, 教授 (10273632)
• Co-Investigator(Kenkyū-buntansha): TAGAMI Shinji 大阪大学, 大学院医学系研究科, 助教 (40362735) ; MORIHARA Takashi 大阪大学, 大学院医学家研究科, 助教 (90403196)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: アルツハイマー病 / タウオパチー / 小胞体ストレス / タウ / ユビキチン

Outline of Final Research Achievements

We show that ER stress, induced by glucose deprivation or chemicals, increases total endogenous tau protein in cultured neurons and primary cultured neurons. Under ER stress, no significant differences were observed in the transcription f tau, and no differences were observed in the translation of tau with or ithout the 50-untranslated region (50UTR) of tau. In contrast, the degradation rate of tau was decreased by 20% under ER stress. ER stress reduced the binding between tau and carboxyl terminus of Hsc70-interacting protein (CHIP), biquitin E3 ligase for tau. These results suggest that ER stress increases total tau protein and its mechanism is due to the decrease in the binding between tau and CHIP, which delays the degradation of tau protein through the ubiquitin proteasome pathway. This mechanism may provide clue to treatment for tauopathy.

Free Research Field

精神医学、神経化学