skip to main content

Organic Chemistry Seminar

Wednesday, February 20, 2019
4:00pm to 5:00pm
Add to Cal
Noyes 153 (J. Holmes Sturdivant Lecture Hall)
Chirality, Alzheimer's Disease and Amyloid Beta
Jevgenij Raskatov, Assistant Professor of Chemistry, Department of Chemistry and Biochemistry, University of California, Santa Cruz,

Aggregation-prone polypeptides are produced by living systems, often as cleavage products of substantially larger protein precursors. Whereas their functions in health are challenging to study and not always well understood, an imbalance between their production and clearance can produce diverse pathological conditions, including Alzheimer's Disease. The believed seminal etiological agent of AD, amyloid beta forms aggregates of different size and shape, with distinctions frequently made between oligomers, protofibrils and fibrils. Oligomers are believed to be particularly harmful, whereas fibrils appear to represent an aggregation endpoint that may be relatively benign.

Through stereochemical arguments, we envisioned that racemic amyloid beta should exhibit increased fibril formation and reduced toxicity. We synthesized the two enantiomers and found indeed that their equimolar mixture exhibited pronounced acceleration of fibril formation, as compared to the enantiopure counterparts. This led to substantial suppression of oligomer formation and inhibition of toxicity in model cell-based systems. The underlying molecular mechanisms that lead to the differences in biophysical and biological properties observed between enantiopure and racemic Aβ42 remain subject of active research in our laboratory.

For more information, please contact Vicky Brennan by phone at 626-395-6151 or by email at [email protected].