Untangling tau hyperphosphorylation in drug design for neurodegenerative diseases.
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.
Mazanetz
Michael P
MP
Centre for Biomolecular Sciences and School of Pharmacy, University of Nottingham, University Park, Nottingham NG7 2RD, UK.
Fischer
Peter M
PM
D000818:Animals; D001682:Biological Availability; D001921:Brain / Q000378:metabolism; D051360:Cyclin-Dependent Kinase 5 / Q000037:antagonists & inhibitors* / Q000737:chemistry; D015195:Drug Design; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors* / Q000737:chemistry; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors* / Q000737:chemistry; D019636:Neurodegenerative Diseases / Q000188:drug therapy*; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016875:tau Proteins / Q000378:metabolism*
D047428:Protein Kinase Inhibitors; D016875:tau Proteins; D051360:Cyclin-Dependent Kinase 5; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D019950:Mitogen-Activated Protein Kinase 1; D038362:Glycogen Synthase Kinase 3