Gamma-Secretase as a Pharmacological Target in Alzheimer Disease Research: When, Why and How?

Alzheimer disease (AD) is characterized by excessive deposition of amyloid β-peptides (Aβ peptides) in the form of senile plaques as well as neurofibrillary tangles (NFTs) in the brain. In the amyloidogenic pathway, the amyloid-β precursor protein (APP) is cleaved by β-secretase first, followed by γ-secretase cleavage producing therefore Aβ. This review summarizes the recent findings in the AD field and focuses on the different γ-secretase inhibitors that have been developed as a therapeutic approach toward AD.