Untangling tau hyperphosphorylation in drug design for neurodegenerative diseases

Aggregation of hyperphosphorylated tau is involved in neurodegeneration in Alzheimer's disease and other disorders. The authors discuss the progress in the design of selective kinase inhibitors that suppress tau hyperphosphorylation as a therapeutic strategy for neurodegenerative tauopathies. 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.