Assistant Professor, Biophysical Chemistry
Binghamton University
The State University of New York

Title: Understanding the Neuronal Cellular Membrane Disruption induced by the
Early-stage Aggregation of Beta-Amyloid Peptides

Abstract

The neuronal cellular toxicity of beta-amyloid (Abeta) peptides is
considered as a main pathology in Alzheimer’s Diseases (AD). The
cellular membrane disruption, which may be induced by the amyloidosis
process of Abeta, is an important contribution to the molecular
mechanism of the peptides’ neurotoxicity. However, the Abeta-induced
membrane disruption process is highly heterogeneous, bringing major
challenge for molecular mechanistic studies using high-resolution
techniques such as the solid-state nuclear magnetic resonance (ssNMR)
spectroscopy. The long-term goal of our research is to resolve the
heterogeneity problem in the Abeta-induced neuronal cellular membrane
disruption. We have recently developed protocols to generate model
phospholipid bilayer systems to reduce such heterogeneity by
controlling the absolute peptide concentrations as well as the
peptide-to-lipid molar ratio. The results showed that it was possible
to generate individual Abeta-bilayer model systems with distinct
predominant membrane disruption effects and structurally homogeneous
endpoint Abeta aggregates, which were either on or off the pathway of
fibrillation. The most recent efforts extends the studies from simple
model bilayers to more complicated bilayers and the
rat-brain-extracted synaptic plasma membranes with different ages.