期刊
NEUROSCIENTIST
卷 17, 期 2, 页码 163-173出版社
SAGE PUBLICATIONS INC
DOI: 10.1177/1073858410381532
关键词
sink hypothesis; amyloid; LRP; RAGE; BBB; Alzheimer's disease
资金
- Ministry of Science and Technology of China [2006CB500706, 2009CB941301]
- National Science Foundation of China (NSFC) [30670658, 30370455, 30470542]
- Peking University
- Ministry of Education
Amyloid beta (A beta) plaque, comprised mainly by A beta peptides, is an important pathology of Alzheimer's brains. Major efforts have been devoted to targeting this neurotoxic A beta peptide for discovering disease-modifying treatments for Alzheimer's disease. Inasmuch as A beta is found in both the brain and the periphery, it is hypothesized that there is some form of equilibrium for the A beta in the brain and the periphery such that A beta can be transported across the blood-brain barrier. By modulating the periphery A beta levels, it is predicted that the brain A beta levels will undergo concomitant changes, forming the basis of the sink hypothesis for A beta lowering strategies. In this review, the significance and implication of this sink hypothesis as well as how the sink hypothesis may contribute to the recent A beta-based drug discovery in AD are discussed. Ultimately, the validity of the sink hypothesis will be resolved when the appropriate A beta agents are being tested in the clinic.
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