2020 Fiscal Year Final Research Report
Elucidation of the pathogenic mechanism of neurodegenerative diseases related to abnormal regulation of isomerization of proline
Project/Area Number |
19K23976
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Research Category |
Grant-in-Aid for Research Activity Start-up
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Allocation Type | Multi-year Fund |
Review Section |
0902:General internal medicine and related fields
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Research Institution | Nara Medical University |
Principal Investigator |
Nakanishi Mari 奈良県立医科大学, 医学部, 助教 (40850102)
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Project Period (FY) |
2019-08-30 – 2021-03-31
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Keywords | ALS / LCドメイン / PRポリジペプチド / PPIase |
Outline of Final Research Achievements |
It has become clear that dysfunction of the LC domain is associated with neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS), and many gene mutations in the LC domain occur in proline. Therefore, when the polymerization was evaluated by the hydrogel binding assay under various conditions, it was shown that the polymerization was controlled. There is also a repetitive sequence of C9orf72, the most common genetic abnormality in familial ALS. Therefore, when the effect on phase separation control was evaluated, polymerization was promoted. This indicates that ALS-related genetic abnormalities cause dysregulation of the LC domain.
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Free Research Field |
医学
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Academic Significance and Societal Importance of the Research Achievements |
LCドメインを有するタンパク質のプロリン変異を含む疾患由来変異の解析と、プロリンの異性化を制御しているPPIaseの構造解析を行うことにより、LCドメインに遺伝子異常を持つ神経変性疾患の病態機序の解明を目指している。そのことが治療方法と薬の開発につながり、本研究での成果がそのための第一歩だと考える。
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