2012 Fiscal Year Final Research Report
Analysis of cascade of neuronal cell death for TDP-43 in sporadic amyotrophic lateral sclerosis
| Project/Area Number |
23790977
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Neurology
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| Research Institution | The University of Tokyo |
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Principal Investigator |
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| Project Period (FY) |
2011 – 2012
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| Keywords | TDP-43 / ADAR2 / AMPA 受容体 / GluA2 / RNA 編集 / 筋萎縮性側索硬化症 / 神経細胞死 / Calpain |
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| Research Abstract |
We found that ADAR2-negative motor neurons in the spinal cord showed TDP-43 pathology in conditional ADAR2 knockout (AR2) mice, a mechanistic ALS model in which the ADAR2 gene is targeted in cholinergic neurons including motor neurons. Calpain, a Ca2+-dependent serine protease, was activated in motor neurons devoid of ADAR2 activity express abnormally Ca2+-permeable AMPA receptors that contain Q/R site-unedited GluA2. Moreover, calpain specifically cleaved TDP-43 into aggregation-prone fragments in the lysates of cultured cells.
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