Jevgenij Raskatov

Jevgenij Raskatov

Assistant Professor
University of California at Santa Cruz
Santa Cruz, CA
USA
 jraskato@ucsc.edu

Abstract

Chirality, Alzheimer’s Disease and Amyloid Beta

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 argu¬ments, 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 coun¬ter¬parts. 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.

Lecture Images

Jevgenij Raskatov presenting at APS2019 Jevgenij Raskatov presenting at APS2019 Jevgenij Raskatov presenting at APS2019