Natural product extracts that reduce accumulation of the Alzheimer's amyloid beta peptide: selective reduction in A beta42.
Alzheimer's disease (AD) is the most common form of dementia in the elderly. Without a treatment that significantly delays the progression of the disease over 14 million Americans are likely to be affected with AD by the middle of the 21st Century, presenting an enormous economic and social burden. Evidence gathered over the last two decades has implicated the abnormal accumulation of A beta, in particular the longer more amyloidogenic form A beta42, as a potential causative agent in the disease. To screen for compounds that reduce A beta accumulation we have established several high throughput, cell based screens capable of the sensitive and selective detection of A beta40 and A beta42. Using these screens we have analyzed a proprietary library of natural product extracts for their ability to influence A beta accumulation. Using this approach, we have identified several agents capable of influencing total A beta concentration. In addition, we have identified one extract that selectively reduces A beta42. Intracerebroventricular administration of this agent to mice results in a selective reduction in A beta42 in the brain.
Yager
Debra
D
Mayo Clinic Jacksonville, FL 32224, USA.
Watson
Mona
M
Healy
Brent
B
Eckman
Elizabeth A
EA
Eckman
Christopher B
CB
D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D002470:Cell Survival; D002478:Cells, Cultured; D004353:Drug Evaluation, Preclinical; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D051379:Mice; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010446:Peptide Fragments / Q000378:metabolism
D016229:Amyloid beta-Peptides; D018696:Neuroprotective Agents; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42)