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2023 Fiscal Year Final Research Report

Elucidation of the pathomechanism in developmental and epileptic encephalopathy related to NSF

Research Project

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Project/Area Number 21K15863
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 52050:Embryonic medicine and pediatrics-related
Research InstitutionKyoto University

Principal Investigator

Atsushi Yokoyama  京都大学, 医学研究科, 助教 (90529447)

Project Period (FY) 2021-04-01 – 2024-03-31
Keywords発達性てんかん性脳症 / NSF / 小胞分泌 / オートファジー
Outline of Final Research Achievements

Membrane fusion is involved in a variety of intracellular physiological processes. In order for the membranes to fuse, the SNARE proteins on each membrane need to form a complex. The SNARE complex is dissolved by NSF and recycled in the next membrane fission. Alterations in the NSF gene were identified in patients with developmental and epileptic encephalopathy (DEE) in infancy. This study analyzed the function of the altered NSF using the patient's iPS cells. As a result, it was suggested that the pathomechanism of neurodegeneration in NSF-related DEE may be associated with an abnormally activated mTOR pathway and disrupted autophagy.

Free Research Field

小児神経学

Academic Significance and Societal Importance of the Research Achievements

NSF遺伝子は発達性てんかん性脳症の新規の原因として2019年に報告されたが、その病態背景は明らかにはなっていなかった。今回、NSF遺伝子の変化によって、小胞分泌において膜蛋白リサイクルが障害されていること、mTOR経路の過剰な活性化やオートファジー障害が神経変性に関与していることが示唆された。また、mTOR経路を阻害するラパマイシンが治療薬となる可能性も示唆された。NSF関連発達性てんかん性脳症の病態の一部を明らかにし、治療薬候補を同定したてんにおいて学術的意義があると考えられる。

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Published: 2025-01-30  

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