Centre for Research on Biomolecular Interactions presents Assoc. Prof. Kagan Kerman, Department of Physical & Environmental Sciences, University of Toronto at Scarborough

Talk Title: "Electrochemical methods to understand amyloid-β aggregation kinetics in the presence of metals"

Abstract:

Amyloid-β (Aβ) peptide is the major component of senile plaques found in Alzheimer's disease (AD) patients' brains. Genetic, biochemical and transgenic animal tests have shown Aβ to be a major causative factor for the disease. During the process of Aβ aggregation, the formation of oligomeric species has been associated with toxicity.¹ Although there are many different targets in the amelioration of the negative effects of AD, the approach that has been most successful is the inhibition, reversion and elimination of Aβ aggregation.¹ Metal ions such as Fe(III), Cu(II), Zn(II) and Al(III) were shown to generally modulate the formation of amyloid plaques and facilitate the production of reactive oxygen species.² Small molecules like epigallocatechin gallate (EGCG)³ are potential candidates that can modulate misfolding of proteins. Electrochemical impedance spectroscopy and voltammetry were utilized to measure how EGCG and metal ions interact with the aggregation process of Aβ. Aβ fibril 'seeds' were prepared in the presence of different modulators. These 'seeds' were then immobilized on their corresponding chip surfaces via an amide bond. Exposure of Aβ monomers over these fibril 'seeds' then resulted in the elongation of Aβ in a nucleation-dependent manner. It was found that the metal ions induced the aggregation of Aβ, while EGCG inhibited the Aβ growth.⁴ Surface plasmon resonance, Thioflavin-T fluorescence, and microscopy results supported our findings. Electrochemical methods are versatile platforms that are promising in the development of multiplexed drug screening assays for AD
REFERENCES
1. Soto, C., Mol. Med. Today 1999, 5, 343-350.
2. Adlard, P.A.; Bush, A.I. J. Alzheimers Dis. 2006, 10, 145-163.
3. Bieschke, J.; Russ, J.; Friedrich, R. P.; Ehrnhoefer, D. E.; Wobst, H.; Neugebauer, K.; Wanker, E. E., Proc. Natl. Acad. Sci. USA 2010, 107, 7710-7715.
4. Zhang, B.; Cheng, X.R.; da Silva, I.S.; Hung, V.W.; Veloso, A.J.; Angnes, L.; Kerman, K. Metallomics 2013, 5, 259-264.

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