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Review

Nature Reviews Drug Discovery 6, 464–479 (1 June 2007) | doi:10.1038/nrd2111

Untangling tau hyperphosphorylation in drug design for neurodegenerative diseases

Michael P. Mazanetz & Peter M. Fischer

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 — GSK3β, CDK5 and ERK2 — as drug targets and describe progress in the design of inhibitors for these kinases.