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2016 Fiscal Year Final Research Report

Selective protein degradation with the aim of developing therapies for neurodegenarative diseases

Research Project

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Project/Area Number 26293207
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field Neurology
Research InstitutionUniversity of Occupational and Environmental Health, Japan

Principal Investigator

Adachi Hiroaki  産業医科大学, 医学部, 教授 (40432257)

Co-Investigator(Kenkyū-buntansha) 岡田 和将  産業医科大学, 医学部, 講師 (30341499)
岩中 行己男  産業医科大学, 医学部, 助教 (60590461)
橋本 智代  産業医科大学, 医学部, 助教 (70425685)
黄 哲  産業医科大学, 医学部, 助教 (30745112)
Project Period (FY) 2014-04-01 – 2017-03-31
Keywords神経変性疾患 / オートファジー / 分子シャペロン / ユビキチン・プロテアソーム系 / TFEB / HIKESHI / ポリグルタミン病 / 球脊髄性筋萎縮症
Outline of Final Research Achievements

The transcription factor EB (TFEB) has been reported to regulate autophagy by upregulating genes that belong to the coordinated lysosomal expression and regulation (CLEAR) network, thereby controlling lysosomal biogenesis. Hikeshi is essential for the entry of the Hsc70/Hsp70 (Hsp70s) to the nucleus under stress condition. We examined the effects of the overexpression of TFEB and Hikeshi in cultured cell models of neurodegenerative diseases. Neuronal cells were transfected with plasmids encoding mutant androgen receptor, huntingtin, ataxin-1, ataxin-3, Hikeshi and TFEB. The overexpression of TFEB and Hikeshi decreased the expression of each causative protein in the neuronal cell models. Hikeshi could interact with TFEB and enhance the degradation of the disease-causative proteins. On the other hand, reduction of TFEB and Hikeshi slows the turnover of mutant proteins. These findings demonstrated that TFEB and Hikeshi influence the degradation of the disease-causative proteins.

Free Research Field

神経内科学

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Published: 2018-03-22  

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