Involvement of cell stress-related translational mechanisms in the pathogenesis of frontotemporal dementia.

2023 Fiscal Year Final Research Report

• Project/Area Number: 19K17111
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 52030:Psychiatry-related
• Research Institution: Saitama University
• Principal Investigator: Omi Tsubasa 埼玉大学, 教育機構, 准教授 (00752122)
• Project Period (FY): 2019-04-01 – 2024-03-31
• Keywords: C9orf72 / non-AUG翻訳 / 翻訳開始因子

Outline of Final Research Achievements

G4C2 repeat expansion in the C9orf72 gene, is translated into disease characterizing dipeptide repeat proteins via repeat-associated non-AUG (RAN) translation, has been shown to cause frontotemporal lobar degeneration and amyotrophic lateral sclerosis. TDP-43 and FUS-positive intracellular are thought to be insoluble stress granules, suggesting the association between cellular stress responses. In order to clarify the association between the translation mechanism selectively induced under stress response and DPR production, we validated the identification of translation initiation factors or their regulators used by non-AUG translation, whose regulatory mechanism is still unresolved. Currently, we are verifying and analyzing the mechanism of action of the factors we have identified, and are aiming to compile our research results for submission to an English-language journal.

Free Research Field

精神医学

Academic Significance and Societal Importance of the Research Achievements

本研究では、細胞にストレスがかかった際に選択的に誘導される翻訳機構と、前頭側頭型認知症の病態の一つとして考えられている異常タンパク質産生の関連性について検証を行った。その結果、この病態に関連する分子メカニズムの一端を明らかにし、将来的に前頭側頭型認知症の新規治療法開発につながる可能性を秘めた知見を得た。