Design of Inhibitors of Alzheimer Amyloid-ß Peptide Aggregation

Joan-Emma Shea
UC Santa Barbara

Alzheimer’s disease belongs to a class of neurodegenerative diseases associated with the presence of amyloid deposits in the brain. These deposits consist, in the case of Alzheimer's disease, of aggregates of amyloid-beta (Aß) peptides. An attractive therapeutic approach to combat amyloid diseases lies in the development of strategies to inhibit or reverse aggregation. We consider the 16-22 fragment of the (Aß) peptide, the shortest sequence of Alzheimer Aß peptides capable of forming toxic fibrils. An N-methylated version of this peptide has recently been shown to inhibit fibrillogenesis and disassemble Aß fibrils. We present molecular dynamics simulations of the interaction of this inhibitor peptide with a model Aß fibril and propose a novel mechanism for its mode of action. Implications for the design of further amyloid inhibitors will be discussed.

Presentation (PowerPoint File)

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