Protein kinases CK1 and CK2 as new targets for neurodegenerative diseases.
Following the discovery of the human kinome, protein kinases have become the second most important group of drug targets as they can be modulated by small ligand molecules. Moreover, orally active protein kinase inhibitors have recently reached the market and there are many more in clinical trials. The lack of treatments for neurodegenerative diseases has increased human and financial efforts in the search for new therapeutic targets that could provide new effective drug candidates. The importance of kinases in the molecular pathway of neuronal survival is under study, but different key pathways have been described. New roles for the old casein kinases 1 and 2, currently known as protein kinases CK1 and CK2, have recently been discovered in the molecular pathology of different neurodegenerative disorders, such as Alzheimer's and Parkinson's diseases and amyotrophic lateral sclerosis. The search for specific inhibitors of these enzymes has become an important challenge for the treatment of these devastating diseases. The role of these two kinases in the molecular pathology of different neurodegenerative diseases together with different chemical families that are able to more or less specifically inhibit CK1 and CK2 are discussed in this review.
Perez
Daniel I
DI
Instituto de Quimica Medica-CSIC, Juan de la Cierva 3, 28006 Madrid, Spain.
Gil
Carmen
C
Martinez
Ana
A
D000544:Alzheimer Disease / Q000188:drug therapy; D000690:Amyotrophic Lateral Sclerosis / Q000188:drug therapy; D000818:Animals; D001667:Binding, Competitive; D047389:Casein Kinase I / Q000378:metabolism*; D047390:Casein Kinase II / Q000378:metabolism*; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D051379:Mice; D019636:Neurodegenerative Diseases / Q000188:drug therapy* / Q000201:enzymology; D010300:Parkinson Disease / Q000188:drug therapy; D010766:Phosphorylation; D051381:Rats
D004791:Enzyme Inhibitors; D047389:Casein Kinase I; D047390:Casein Kinase II