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Alterations in Glucose Metabolism Induce Hypothermia Leading to Tau Hyperphosphorylation through Differential Inhibition of Kinase and Phosphatase Activities: Implications for Alzheimer's Disease

Authors :
Tomohiro Miyasaka
Akihiko Takashima
De Hua Chui
Emmanuel Planel
Ohoshi Murayama
Yoshitaka Tatebayashi
Koichi Ishiguro
Thomas Launey
Shinji Sato
Kentaro Tanemura
Publication Year :
2004
Publisher :
Society for Neuroscience, 2004.

Abstract

Alzheimer's disease (AD) brains contain neurofibrillary tangles (NFTs) composed of abnormally hyperphosphorylated tau protein. Regional reductions in cerebral glucose metabolism correlating to NFT densities have been reported in AD brains. Assuming that reduced glucose metabolism might cause abnormal tau hyperphosphorylation, we inducedin vivoalterations of glucose metabolism in mice by starvation or intraperitoneal injections of either insulin or deoxyglucose. We found that the treatments led to abnormal tau hyperphosphorylation with patterns resembling those in early AD brains and also resulted in hypothermia. Surprisingly, tau hyperphosphorylation could be traced down to a differential effect of low temperatures on kinase and phosphatase activities. These data indicate that abnormal tau hyperphosphorylation is associated with altered glucose metabolism through hypothermia. Our results imply that serine-threonine protein phosphatase 2A plays a major role in regulating tau phosphorylation in the adult brain and providein vivoevidence for its crucial role in abnormal tau hyperphosphorylation in AD.

Details

Language :
English
Database :
OpenAIRE
Accession number :
edsair.doi.dedup.....7fbe0679040daccd3c64c90a7ad4ab7b