Potential use of γ-secretase modulators in the treatment of Alzheimer disease.
Although significant progress has occurred in the past 20 years regarding our understanding of Alzheimer disease pathogenesis, we have yet to identify disease-modifying therapeutics capable of substantially altering the clinical course of this prevalent neurodegenerative disease. In this short review, we discuss 2 approaches that are currently being tested clinically (γ-secretase inhibition and γ-secretase modulation) and emphasize the significant differences between these 2 therapeutic approaches. We also discuss certain genetic- and biomarker-based translational and clinical trial paradigms that may assist in developing a useful therapeutic agent.
Department of Neurosciences, University of California, San Diego, School of Medicine, La Jolla, CA 92063, USA. slwagner@ucsd.edu
Steven L
SL
Wagner
Rudolph E
RE
Tanzi
William C
WC
Mobley
Douglas
D
Galasko
D000544:Alzheimer Disease / Q000201:enzymology* / Q000628:therapy*; D053829:Amyloid Precursor Protein Secretases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D006801:Humans
D053829:Amyloid Precursor Protein Secretases