Abstract
Aggregation of hyperphosphorylated tau is one of the characteristic neuropathological lesions of Alzheimer's disease and other neurodegenerative disorders. Pharmacological modulation of tau hyperphosphorylation might represent a valid and feasible therapeutic strategy for such disorders. Here, we consider recent evidence supporting the validity of the three most relevant kinases affecting tau hyperphosphorylation - GSK3beta, CDK5 and ERK2 - as drug targets and describe progress in the design of inhibitors for these kinases.
MeSH terms
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Animals
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Biological Availability
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Brain / metabolism
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Cyclin-Dependent Kinase 5 / antagonists & inhibitors*
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Cyclin-Dependent Kinase 5 / chemistry
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Drug Design*
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Glycogen Synthase Kinase 3 / antagonists & inhibitors*
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Glycogen Synthase Kinase 3 / chemistry
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Glycogen Synthase Kinase 3 beta
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Humans
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Mitogen-Activated Protein Kinase 1 / antagonists & inhibitors*
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Mitogen-Activated Protein Kinase 1 / chemistry
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Neurodegenerative Diseases / drug therapy*
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Phosphorylation
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Protein Kinase Inhibitors / pharmacokinetics
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Protein Kinase Inhibitors / therapeutic use*
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tau Proteins / metabolism*
Substances
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Protein Kinase Inhibitors
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tau Proteins
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Cyclin-Dependent Kinase 5
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GSK3B protein, human
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Glycogen Synthase Kinase 3 beta
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Mitogen-Activated Protein Kinase 1
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Glycogen Synthase Kinase 3