Revealing the molecular mechanism of regulating SOD1 proteostasis by zinc-related genes for understanding ALS pathogenesis

2017 Fiscal Year Final Research Report

• Project/Area Number: 16K18513
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Functional biochemistry
• Research Institution: The University of Tokyo
• Principal Investigator: Homma Kengo 東京大学, 大学院薬学系研究科(薬学部), 特任研究員 (60708171)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Keywords: 亜鉛 / SOD1 / ALS / 亜鉛トランスポーター

Outline of Final Research Achievements

ALS is a devastating neurodegenerative disease characterized by the selective motoneuron death. We have previously reported that SOD1 mutants interact with Derlin-1, leading to the motoneuron death. In addition, we have found that the zinc depletion induced the conformational change of wild-type SOD1 (SOD1WT) and the interaction between SOD1WT and Derlin-1. To evaluate the possibility that the conformationally-disordered SOD1WT could be involved in the pathogenesis of SOD1 mutation-negative ALS, we investigated the molecular mechanism of SOD1WT conformational change.
The analysis of ZIP13, a zinc transporter, that was identified as a mediator of zinc depletion-induced SOD1WT conformational change revealed the essential role of the Golgi apparatus in zinc depletion-induced SOD1WT conformational change.

Free Research Field

分子生物学