A number of human protein misfolding disorders, including Alzheimer's disease (AD), are closely related to the accumulation of beta-sheet-rich amyloid fibrils or aggregates. Neuronal toxicity in AD has been linked to the interactions of amyloid-beta (Aβ) with metals, especially Zn2+, Cu2+, and Fe3+, which leads to the production of reactive oxygen species. Nucleation-dependent Aβ aggregation, or "seeding", is thought to propagate fibril formation. In this surface plasmon resonance imaging (SPRi) study, we have shown that the fibril seeds formed with the incubation of Aβ in the presence of metals are better at promoting monomer elongation compared to Aβ alone or in the presence of a well-described polyphenol, (-)-epigallocatechin-3-gallate (EGCG). This is a novel attempt to simultaneously monitor the effects of multiple modulators on fibril elongation using a single chip. EGCG was shown in transmission electron microscopy (TEM) and thioflavin T (ThT) studies to promote the formation of off-pathway, highly stable unstructured oligomers, supporting the SPRi results. These findings suggest that SPRi provides a promising platform as a screening tool for small molecules that can affect the aggregation pathways in neurodegenerative diseases.
Martic joined Oakland University last fall. She obtained her B.S. from Bishop’s University and her M.S. from McMaster University, and then received her Ph.D. degree in 2009 in bioorganometallic chemistry from the Queen’s University in Ontario, Canada. She worked as a postdoc in bioanalytical chemistry in the group of Heinz-Bernhard Kraatz at the University of Western Ontario and the University of Toronto, Scarborough. Research in Martic’s lab lies at the interface of chemistry and biology, and focuses on designing functional bioconjugates for understanding fundamental biological processes. Current projects combine organic synthesis and analytical chemistry for probing the biomolecular interactions in solution and on surfaces.
An article by Assistant Professor Sanela Martic, of the Department of Chemistry, appeared in the February 2013 issue of the journal Analytical Chemistry.
Created by Brad Roth (roth@oakland.edu) on Thursday, March 21, 2013 Modified by Brad Roth (roth@oakland.edu) on Thursday, March 21, 2013 Article Start Date: Thursday, March 21, 2013