Journal
NEUROBIOLOGY OF DISEASE
Volume 46, Issue 3, Pages 701-709Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.nbd.2012.03.013
Keywords
Alzheimer's disease; beta-Amyloid; Peptide; Cytotoxicity; Memory deficits; A beta clearance
Categories
Funding
- National Natural Science Foundation of China (NSFC) [30971012, 81171014]
- National Science and Technology Major Projects of New Drugs [2012ZX09103301-001]
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Alzheimer's disease (AD) is characterized by progressive memory loss due to extracellular senile plaques and intracellular neurofibrillary tangles. The toxic beta-amyloid (A beta) aggregates that form in AD can induce the overproduction of reactive oxygen species (ROS), nitric oxide (NO), and proinflammatory cytokines. These A beta aggregates likely play a pivotal role in the onset and progression of AD. Reducing A beta generation, inhibiting A beta toxicity, and improving A beta clearance are promising therapeutic strategies for AD. The present paper is the first to reveal a heptapeptide (XD4) isolated from a Ph.D.-C7C library through phage display that significantly inhibited A beta cytotoxicity, increased the microglial phagocytosis of A beta, decreased the A beta-induced generation of ROS and NO, and attenuated the disequilibrium of calcium homeostasis in vitro. Remarkably, XD4 also attenuated memory deficits in beta-amyloid precursor protein/presenilin 1 (APPswe/PS1dE9) transgenic mice, and reduced amyloid plaque burden and A beta 40/42 levels. The results of the present study indicate that this peptide, which specifically targets A beta, may be a promising new therapy for patients exhibiting cognitive impairment and increased A beta burden. (C) 2012 Elsevier Inc. All rights reserved.
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