Recent developments of structure based beta-secretase inhibitors for Alzheimer's disease.
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.
Ghosh
Aurn K
AK
Departments of Chemistry and Medicinal Chemistry, Purdue University, West Lafayette, IN 47907, USA. akghosh@purdue.edu
Kumaragurubaran
Nagaswamy
N
Tang
Jordan
J
D000544:Alzheimer Disease / Q000188:drug therapy*; D000595:Amino Acid Sequence; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; D010450:Endopeptidases / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D013329:Structure-Activity Relationship
D004791:Enzyme Inhibitors; D053829:Amyloid Precursor Protein Secretases; D010450:Endopeptidases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human