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KMID : 0606920120200030245
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Biomolecules & Therapeutics
2012 Volume.20 No. 3 p.245 ~ p.255
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Mechanisms of Amyloid-β Peptide Clearance: Potential Therapeutic Targets for Alzheimer’s Disease
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Yoon Sang-Sun
Jo Sang-Mee-Ahn
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Abstract
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Amyloid-β peptide (Aβ) is still best known as a molecule to cause Alzheimer’s disease (AD) through accumulation and deposition within the frontal cortex and hippocampus in the brain. Thus, strategies on developing AD drugs have been focused on the reduc-tion of Aβ in the brain. Since accumulation of Aβ depends on the rate of its synthesis and clearance, the metabolic pathway of Aβ in the brain and the whole body should be carefully explored for AD research. Although the synthetic pathway of Aβ is equally important, we summarize primarily the clearance pathway in this paper because the former has been extensively reviewed in previous studies. The clearance of Aβ from the brain is accomplished by several mechanisms which include non-enzymatic and enzymatic pathways. Nonenzymatic pathway includes interstitial fluid drainage, uptake by microglial phagocytosis, and transport across the blood vessel walls into the circulation. Multiple Aβ-degrading enzymes (ADE) implicated in the clearance process have been identified, which include neprilysin, insulin-degrading enzyme, matrix metalloproteinase-9, glutamate carboxypeptidase II and others. A series of studies on Aβ clearance mechanism provide new insight into the pathogenesis of AD at the molecular level and suggest a new target for the development of novel therapeutics.
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KEYWORD
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Amyloid-β peptide, Amyloid-β peptide degrading enzyme, Alzheimer’s disease, Clearance, Proteases
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