2014 Fiscal Year Final Research Report
Role of Hsp70 and its related molecules in neuronal death
Project/Area Number |
24659540
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Research Category |
Grant-in-Aid for Challenging Exploratory Research
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Allocation Type | Multi-year Fund |
Research Field |
Psychiatric science
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Research Institution | Kanazawa University |
Principal Investigator |
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Co-Investigator(Kenkyū-buntansha) |
YAMASHIMA Tetsumori 金沢大学, 医学系, 准教授 (60135077)
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Project Period (FY) |
2012-04-01 – 2015-03-31
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Keywords | 認知症 |
Outline of Final Research Achievements |
Using the monkey experimental paradigm, previously we reported that calpain-mediated cleavage of oxidized Hsp70.1 causes neurodegeneration in the hippocampal CA1 sector. However, the molecular mechanisms of the lysosomal destabilization/stabilization have not been elucidated. To elucidate whether regulation of lysosomal ASM could affect the neuronal fate, we analyzed Hsp70.1-BMP binding and ASM activity. We showed that Hsp70.1 being localized at the lysosomal membrane, lysosomal lipid BMP levels, and the lipid binding domain of Hsp70.1 are crucial for Hsp70.1- BMP binding. Calpain activation and a concomitant decrease in the lysosomal membrane localization of Hsp70.1 and BMP levels may diminish Hsp70.1-BMP binding, resulting in decreased ASM activity and lysosomal rupture with leakage of cathepsin B into the cytosol. Regulation of ASM activation in vivo by Hsp70.1-BMP affects lysosomal stability and neuronal survival or death after ischemia/reperfusion.
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Free Research Field |
神経精神医学
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