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2014 Fiscal Year Final Research Report

Analysis of neuronal cell death by ALS-associated misfolded protein aggregation with modulation of cellular RNA homeostasis

Research Project

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Project/Area Number 23770215
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Cell biology
Research InstitutionHokkaido University

Principal Investigator

KITAMURA Akira  北海道大学, 先端生命科学研究科(研究院), 助教 (10580152)

Project Period (FY) 2011 – 2014
KeywordsALS / タンパク質凝集体 / 神経変性疾患 / 細胞内封入体 / RNA / TDP43 / 蛍光相関分光法
Outline of Final Research Achievements

TAR-RNA/DNA binding protein 43 kDa is a disease gene product associated with amyotrophic lateral sclerosis (ALS), a motor neuron disease. In this research, fluorescence correlation spectroscopy (FCS) measurement in cell lysate revealed that a 25 kDa carboxyl-terminal fragment of TDP43 (TDP25) formed aggregation after dissociation of RNA. Next, TDP43 was sequestrated into cytoplasmic inclusion bodies of TDP25 in living cells. Neuronal cells expressing TDP25 showed higher cell death efficiency than that of TDP43. These results suggest that TDP25 may be an aggregation-causative and toxic seed, and RNA may play an important role for inhibition of aggregation-formation of TDP25.

Free Research Field

細胞生物学・生物物理学

URL: 

Published: 2016-06-03  

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