Abstract
The abnormal hyperphosphorylation of tau protein is one of the hallmarks of Alzheimer disease and other tauopathies; as yet the exact role of various tau kinases in this pathology is not fully understood. Here, we show that injection of isoproterenol, an activator of cAMP-dependent kinase (PKA), into rat hippocampus bilaterally results in the activation of PKA, calcium/calmodulin-dependent kinase II and cyclin-dependent kinase-5, inhibition of protein phosphatase-2A, hyperphosphorylation of tau at several Alzheimer-like epitopes and a disturbance of spatial memory retention 48 h after the drug injection. These findings suggest the involvement of PKA and PKA-mediated signaling pathway in the Alzheimer-like tau hyperphosphorylation and memory impairment.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Alzheimer Disease / enzymology
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Animals
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Calcium-Calmodulin-Dependent Protein Kinases / physiology
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Cyclic AMP-Dependent Protein Kinases / metabolism*
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Cyclic AMP-Dependent Protein Kinases / physiology
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Cyclin-Dependent Kinase 5
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Cyclin-Dependent Kinases / metabolism
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Cyclin-Dependent Kinases / physiology
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Hippocampus / drug effects
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Hippocampus / enzymology*
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Injections
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Isoproterenol / administration & dosage
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Memory Disorders / chemically induced
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Memory Disorders / enzymology*
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Phosphorylation / drug effects
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Rats
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Spatial Behavior / drug effects
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tau Proteins / analysis
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tau Proteins / metabolism*
Substances
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tau Proteins
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Cyclin-Dependent Kinase 5
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Cyclic AMP-Dependent Protein Kinases
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Calcium-Calmodulin-Dependent Protein Kinases
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Cdk5 protein, rat
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Cyclin-Dependent Kinases
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Isoproterenol