We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Identification of Antihypertensive Drugs Which Inhibit Amyloid-β Protein Oligomerization.
- Authors
Wei Zhao; Jun Wang; Lap Ho; Ono, Kenjiro; Teplow, David B.; Pasinetti, Giulio M.
- Abstract
Recent studies suggest that certain cardiovascular antihypertensive agents decrease the incidence of Alzheimer's disease. Based on this evidence and the fact that Aβ aggregation into high-molecular-weight-soluble oligomeric Aβ species is known to directly induce cognitive impairment, we tested the possibility that certain antihypertensive compounds may affect the progression of Alzheimer's disease, at least in part by influencing the formation of Aβ oligomers. High throughput screening of 55 commercially available antihypertensive drugs identified four compounds that significantly reduced Aβ_{1-42} oligomerization in a dose dependent manner. These four compounds, furosemide (diuretic), nitrendipine (calcium channel blocker), candesartan cilextil (angiotensin II receptor antagonist) and diazoxide (vasodilator) showed no detectable Aβ lowering activities in primary neuron cultures generated from Tg2576 mouse embryos. However, furosemide, nitrendipine and candesartan cilextil prevented oligomerization of both Aβ_{1-40} and Aβ_{1-42} in vitro. Furosemide also dissociated pre-aggregated Aβ_{1-42} oligomers. Furthermore, short term furosemide treatment resulted in decreased amount of Aβ oligomers in the brain of Tg2576 mice. Our studies suggest that certain antihypertensive compounds may prevent AD-type neuropathology through inhibition of Aβ oligomer formation.
- Publication
Journal of Alzheimer's Disease, 2009, Vol 16, Issue 1, p49
- ISSN
1387-2877
- Publication type
Academic Journal
- DOI
10.3233/JAD-2009-0925