Roles of P bodies and stress granules in the pathogenesis of intranuclear inclusion body disease
| Project/Area Number |
17K07088
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Research Field |
Nerve anatomy/Neuropathology
|
|---|
| Research Institution | Hirosaki University |
|---|
Principal Investigator |
Mori Fumiaki 弘前大学, 医学研究科, 准教授 (60200383)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
三木 康生 弘前大学, 医学研究科, 助教 (30709142)
若林 孝一 弘前大学, 医学研究科, 教授 (50240768)
|
|---|
| Project Period (FY) |
2017-04-01 – 2020-03-31
|
| Project Status |
Completed (Fiscal Year 2019)
|
| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
|
|---|
| Keywords | 核内封入体病 / DIS3L2 / XRN1 / エキソリボヌクレアーゼ / ポリグルタミン病 / 神経変性疾患 / P小体 / ストレス顆粒 / 認知症 |
|---|
| Outline of Final Research Achievements |
mRNA turnover controls gene expression under various conditions in aging and neurodegenerative diseases. Polyglutamine (polyQ) diseases and intranuclear inclusion body disease (INIBD) are neurodegenerative diseases characterized by the formation of nuclear inclusions. Using immunohistochemistry with antibodies against DIS3L2 and XRN1, we examined the brains of patients with polyQ diseases and INIBD and normal control subjects. In controls, immunoreactivity for DIS3L2 and XRN1 was found in the neuronal cytoplasm and neuropil, respectively. In INIBD, immunoreactivity for DIS3L2 and XRN1 was present in neuronal and glial nuclear inclusions. Co-localization of ubiquitin and DIS3L2 or XRN1 was demonstrated in these inclusions. In polyQ diseases, however, nuclear inclusions were immunonegative for DIS3L2 and XRN1. These findings suggest that sequestration of exoribonucleases to nuclear inclusions may be related to the pathogenesis of INIBD.
|
| Academic Significance and Societal Importance of the Research Achievements |
核内封入体病において、さまざまなストレスが、PB小体/ストレス顆粒関連蛋白の発現変動を惹起し、神経細胞ならびにアストログリアの核内にPB/SG関連蛋白が取り込まれ、核内封入体が形成される。特に成人型核内封入体病では、アストロサイトでの核内封入体形成が高頻度に起こることから、アストロサイトによる神経細胞ならびに軸索への栄養供給ならびに保護作用が阻害される可能性が考えられる。本研究で検討するPB小体/ストレス顆粒関連蛋白の動態は核内封入体病の病理発生機序の解明に役立ち、PB小体/ストレス顆粒関連蛋白の制御が神経難病治療に役立つ可能性を提示した。
|
Report
(4 results)
Research Products
(19 results)
-
-
-
-
-
-
[Journal Article] Phosphorylated TDP-43 aggregates in skeletal and cardiac muscle are a marker of myogenic degeneration in amyotrophic lateral sclerosis and various conditions.2019
Author(s)
Mori F, Tada M, Kon T, Miki Y, Tanji K, Kurotaki H, Tomiyama M, Ishihara T, Onodera O, Kakita A, Wakabayashi K.
-
Journal Title
Acta Neuropatholgica Communications
Volume: 7
Issue: 1
Pages: 165-165
DOI
Related Report
Peer Reviewed / Open Access
-
-
-
-
-
-
-
-
-
-
-
-
-
