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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
- 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.
- Subjects :
- Blood Glucose
Male
medicine.medical_specialty
medicine.medical_treatment
Tau protein
Phosphatase
Blotting, Western
Neocortex
tau Proteins
Hypothermia
Carbohydrate metabolism
Deoxyglucose
Body Temperature
Mice
GSK-3
Alzheimer Disease
Internal medicine
Cerebellum
medicine
Phosphoprotein Phosphatases
Animals
Insulin
Protein Phosphatase 2
Phosphorylation
biology
Kinase
General Neuroscience
Cyclin-dependent kinase 5
Phosphotransferases
Protein phosphatase 2
Axons
Phosphoric Monoester Hydrolases
Mice, Inbred C57BL
Endocrinology
Glucose
Starvation
biology.protein
Cellular/Molecular
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....7fbe0679040daccd3c64c90a7ad4ab7b