Advances in the development of kinase inhibitor therapeutics for Alzheimer's disease
Article first published online: 27 FEB 2009
© 2009 Wiley-Liss, Inc.
Drug Development Research
Special Issue: Alzheimer's Disease: A Light at the End of the Tunnel?
Volume 70, Issue 2, pages 125–144, March 2009
How to Cite
Savage, M. J. and Gingrich, D. E. (2009), Advances in the development of kinase inhibitor therapeutics for Alzheimer's disease. Drug Dev. Res., 70: 125–144. doi: 10.1002/ddr.20287
- Issue published online: 19 MAR 2009
- Article first published online: 27 FEB 2009
- cyclin-dependent kinase 5;
- glycogen synthase kinase 3;
- c-Jun N-terminal kinase;
- p38 kinase;
- Casein kinase 1;
- Rho kinase;
- p21-activating kinase;
Pharmaceutical approaches to slow the progression of Alzheimer's disease (AD) have focused primarily on reducing production or increasing clearance of amyloid β peptide (Aβ). Recent clinical trial results question the efficacy of targeting Aβ for treatment of mild to moderate AD, highlighting the need for alternate approaches. With the marketing of eight kinase inhibitors for oncology indications as of 2008 (Gleevec®, Tarceva®, Nexavar®, Sutent®, Rapamune®, Sprycel®, Tasigna®, and Tykerb®) and current clinical trials of more than 150 others for a number of indications, the progress that has been made in improving the selectivity and pharmaceutical properties of this class of compounds suggests that targeting neurodegenerative diseases such as AD may be possible. The present review describes a number of kinase targets for AD that have been studied in relation to tau protein pathology, neuroinflammation and neuron loss, in addition to amyloid pathology. Drug Dev Res 70, 2009. © 2009 Wiley-Liss, Inc.