title: Untangling tau hyperphosphorylation in drug design for neurodegenerative diseases.
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.
authors.affiliation: Centre for Biomolecular Sciences and School of Pharmacy, University of Nottingham, University Park, Nottingham NG7 2RD, UK.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Mazanetz
authors.forename: Peter M
authors.initials: PM
authors.lastname: Fischer
mesh_terms: 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*
chemical_list: 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