Advances in the Development of Kinase Inhibitor Therapeutics for Alzheimer's Disease

Pharmaceutical approaches to slow the progression of Alzheimer's disease (AD) have focused primarily on reducing production or increasing clearance of amyloid beta peptide (A beta). Recent clinical trial results question the efficacy of targeting A beta 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 (R), Tarceva (R), Nexavar (R), Sutent (R), Rapamune (R), Sprycel (R), Tasigna (R), and Tykerb (R)) 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 70:125-144, 2009. (C) 2009 Wiley-Liss, Inc.