Targeted Drug Delivery / Smart Drug Delivery / Drug Targeting
Vahid Khandan; Bahar Firoozabadi; Mohammad Saeid Saeidi
Volume 8, Issue 3 , September 2014, , Pages 229-239
Abstract
A hallmark of Alzheimer disease (the most common type of dementia in the elderly) is the aggregation and deposition of toxic species ranging from small soluble oligomers to insoluble fibril plaques of Amyloid-Beta protein originates from the cleavage of APP by Beta and Gama Secretase (Amyloid Hypothesis). ...
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A hallmark of Alzheimer disease (the most common type of dementia in the elderly) is the aggregation and deposition of toxic species ranging from small soluble oligomers to insoluble fibril plaques of Amyloid-Beta protein originates from the cleavage of APP by Beta and Gama Secretase (Amyloid Hypothesis). An attractive therapeutic approach to treat AD is to identify small ligands capable of binding to A-Beta monomers and reverse its amyloidosis process. Here, a peptide drug having the sequence of GLMVG which has been derived from the C-terminal of A-Beta was used as breaker for a monomer of Beta sheet rich structure. The combination of Docking and Molecular Dynamics methods were used for simulation of drug-receptor interaction. This simulation implied that pentapeptide altered secondary structure of A-Beta monomer and declined its stability. This study proved that pentapeptide is capable to reverse Beta-sheet formation and can be considered as an AD drug in other preclinical studies.