Journal
CHEMICAL BIOLOGY & DRUG DESIGN
Volume 86, Issue 4, Pages 805-812Publisher
WILEY-BLACKWELL
DOI: 10.1111/cbdd.12555
Keywords
Alzheimer's disease; A beta 42; curcumin; docking; drug design; florbetapir; molecular mechanics; molecular simulation; thioflavin T
Funding
- UGC-SAP, India
- TEQIP
- UGC CAS
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Aggregation of -amyloid (A) into oligomers and further into fibrils is hypothesized to be a key factor in pathology of Alzheimer's disease (AD). In this study, mapping and docking were used to study the binding of ligands to protofibrils. It was followed by molecular simulations to understand the differences in interactions of known therapeutic agents such as curcumin, fluorescence-based amyloid staining agents such as thioflavin T, and diagnostic agents such as florbetapir (AV45), with A protofibrils. We show that therapeutic agents bind to and distort the protofibrils, thus causing destabilization or prevention of oligomerization, in contrast to diagnostic agents which bind to but do not distort such structures. This has implications in the rational design of ligands, both for diagnostics and therapeutics of AD.
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