Prospects of -Secretase Inhibitors for the Treatment of Alzheimer's Disease

-Secretase continues to be an attractive drug discovery target for the therapeutic intervention of Alzheimer's disease (AD). This enzyme plays a critical role in the production of neurotoxic -amyloid (A) peptides in the brain. Over the years, extensive research efforts have led to the development of many promising classes of inhibitors against this protease. Many small-molecule, peptidomimetic, and nonpeptide -secretase inhibitors have now overcome the key challenging development hurdles such as selectivity and brain penetration. A number of inhibitors have also shown further promise in reducing brain A and rescuing cognitive decline in animal models. Recently, several -secretase inhibitors have entered into preclinical and phaseI studies, and at least one of these inhibitors has advanced to phaseII/III human trials. The outlook on -secretase inhibitor drugs for the treatment of AD patients is discussed herein.