Treating Alzheimer's disease by inactivating bioactive amyloid beta peptide.
Treating Alzheimer's disease (AD) is one of today's biggest unmet medical needs. The drugs currently available transiently relieve some symptoms but have no significant effects on the progression of the disease. Progress in the past decade suggests that the amyloidogenesis of the inactive monomeric amyloid beta peptide (Abeta) into a subset of toxic Abeta polymers is responsible for neurodegeneration in AD. Not all forms of Abeta aggregates are damaging, for there are patients whose brains accumulated large amounts of Abeta in the form of plaques, but they had no obvious neurodegeneration and symptoms of dementia. Since Abeta can polymerize into many types of polymers or aggregates, the form of Abeta that induces neurodegeneration in AD, defined here as bioactive Abeta, is not clear. Preventing the formation of bioactive Abeta or inactivating previously formed bioactive Abeta is a promising approach for treating AD. This review describes our efforts to develop a cell-based assay for detecting bioactive Abeta, to verify the concept of bioactive Abeta in an animal model of AD and in post mortem brain tissue from AD patients, and to use this assay to screen for drugs that can inactivate bioactive Abeta. These studies show the proof in principle that inactivating bioactive Abeta is a promising approach to treat AD. Several promising compounds that can inactivate bioactive Abeta species are also described.
Liu
Yuanbin
Y
Cellular Neurobiology Laboratory, The Salk Institute for Biological Studies, 10010 N. Torrey Pines Road, La Jolla, California 92037-1099, USA. yliu@salk.edu
Schubert
David
D
D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D006801:Humans; D010446:Peptide Fragments / Q000037:antagonists & inhibitors* / Q000378:metabolism*
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments