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Recent Developments of Structure Based β-Secretase Inhibitors for Alzheimers Disease

[ Vol. 5 , Issue. 16 ]


Aurn K. Ghosh, Nagaswamy Kumaragurubaran and Jordan Tang   Pages 1609 - 1622 ( 14 )


The amyloid-β (Aβ) peptide is the principal components of the senile plaques found in the brains of patients with Alzheimers disease (AD). The poorly soluble 40-42 amino acid peptide, formed from the cleavage of the Ab precursor protein (APP) by two proteases, is believed to play a central role in the pathogenesis of AD. β-Secretase (memapsin 2, BACE1), a membrane-anchored aspartic protease, is responsible for the initial step of APP cleavage leading to the generation of Aβ. Identification and structural determination of β-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 β-secretase inhibitors.


Alzheimer's disease, amyloid-β peptide, β-amyloid precursor protein, β-Secretase, Memapsin 2, aspartyl protease inhibitors, BACE-1, neurodegenerative disease, drug development


Department of Chemistry andMedicinal Chemistry, Purdue University, West Lafayette, IN 47907.

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