• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to project page

2021 Fiscal Year Final Research Report

Elucidation of selective vulnerability in neurodegenerative diseases from the perspective of neuronal diversity acquisition and maintenance

Research Project

  • PDF
Project/Area Number 18K07391
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 51030:Pathophysiologic neuroscience-related
Research InstitutionKyoto University

Principal Investigator

Tanabe Yasuto  京都大学, 医学研究科, 特定准教授 (10311309)

Project Period (FY) 2018-04-01 – 2022-03-31
Keywords筋萎縮側索硬化症 / 神経変性疾患
Outline of Final Research Achievements

Dlk1, the fast-fatigable motor neuron cell-fate determinant among generic motor neuron population during embryonic stages, was persistently expressed in adult spinal cord motor neurons until the middle-ages in mice. Our data suggested that Dlk1 may mediate a nucleocytoplasmic transport to take out presumably senescence-associated genotoxic DNAs into the cytoplasm. Given the increased levels of Dlk1 in MNs of TDP-43 Tg homozygotes when motor symptoms progress and the capability of over-expressed Dlk1 for the induction of TDP-43 aggregate in vitro, increased levels of Dlk1 may enhance the nucleocytoplasmic transport system and trigger the formation of TDP-43 aggregates. In contrast, however, our data did not rule out the possibility that Dlk1-mediated nucleocytoplasmic transport system may contribute to the proper transport of genotoxic nuclear materials including TDP-43 for degradation and to prevent the formation of cytoplasmic TDP-43 aggregates in pathological conditions.

Free Research Field

神経変性疾患 老化 認知症

Academic Significance and Societal Importance of the Research Achievements

神経発生学の進展とともに胎生期においてどのようにして中枢神経系を構成する個々の神経細胞の個性が獲得されるのかについては理解が進んだ。しかしながら一旦獲得された個性がどのような分子メカニズムにより成体において維持されているのかの理解は少ない。さらにはその個性維持機構の破綻がどのような病態発現に結びつくのかに関してもその可能性すら考慮されてはいない。本研究は中枢神経系を構成する神経細胞の個性維持機構の破綻が神経変性疾患の選択的脆弱性に結びつく可能性を示唆した。病態を理解する上での新たな治療戦略を与えると考える。

URL: 

Published: 2023-01-30  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi