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Kinetic control of amyloidogenesis calls for unconventional drugs to fight Alzheimer's disease
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Journal: ACS Chem. Neurosci.
Year: 2020
Volume: 11
Issue: 2
Pages: 103-104
DOI: 10.1021/acschemneuro.9b00676
Type of Publication: Journal Article
Keywords:
Alzheimer’s disease; amyloidogenesis; coarse-grained simulations; fibrillogenesis; molecular dynamics
Abstract:
Computer simulations had predicted that amyloid fibrillogenesis is governed by free energy barriers and kinetic traps (kinetic control), rather than the free energy of the final aggregates. The simulations suggested that the diversity in fibril morphologies can originate from variations in the number of protofilaments which has been confirmed by recent cryo-electron microscopy studies of amyloid-β fibrils derived from brain tissue of Alzheimer's patients. The kinetic control of fibril formation and polymorphism imply that chemical substances with new mechanisms of action are needed to fight Alzheimer's disease.