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Curr Top Med Chem. 2005;5(16):1609-22.

Recent developments of structure based beta-secretase inhibitors for Alzheimer's disease.

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  • 1Departments of Chemistry and Medicinal Chemistry, Purdue University, West Lafayette, IN 47907, USA. akghosh@purdue.edu


The amyloid-beta (Abeta) peptide is the principal components of the senile plaques found in the brains of patients with Alzheimer's disease (AD). The poorly soluble 40-42 amino acid peptide, formed from the cleavage of the Abeta precursor protein (APP) by two proteases, is believed to play a central role in the pathogenesis of AD. Beta-secretase (memapsin 2, BACE1), a membrane-anchored aspartic protease, is responsible for the initial step of APP cleavage leading to the generation of Abeta. Identification and structural determination of beta-secretase have established it to be a primary drug target for AD therapy and stimulated active studies on the inhibitors of this protease. Here we review more recent developments in the design and testing of structure-based beta-secretase inhibitors.

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