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Investigating the interactions of bisphosphonates with amyloid beta (Aβ) proteins
* 1 , 2
1  Ph.D. Candidate, SCHOOL OF PHARMACY, UNIVERSITY OF WATERLOO, ONTARIO, CANADA
2  Associate Professor, Pharmaceutical Sciences, School of Pharmacy, University of Waterloo, ONTARIO, CANADA N2L 3G1
Academic Editor: Jean Jacques Vanden Eynde

Abstract:

The unmet therapeutic need for a devastating neurodegenerative disorder, Alzheimer’s disease (AD), which is marked by the deposition of beta-amyloid (Aβ) plaques in the brain - mandates the development of novel anti-Aβ therapies. We investigated the drug-repurposing potential of the bisphosphonate (BPs) class of drugs as anti-Aβ agents. It is known that women are more prone to get AD and are also observed to suffer from osteoporosis after menopause. Therefore, we determined the interactions of BPs with Aβ proteins. The anti-Aβ-aggregation activity against the Aβ40 peptide was evaluated by conducting fluorescence aggregation kinetic studies, transmission electron microscopy (TEM), and computational modeling. Preliminary results suggested that BPs exhibit anti-Aβ activity. Risedronate and alendronate were identified as promising inhibitors of Aβ aggregation. Molecular docking studies for the dimer model of Aβ40 peptide indicated that both risedronate and alendronate showed interactions in the aggregation-prone region of the dimer peptide model. These studies demonstrate that BPs exhibit anti-Aβ activity in vitro and can be used to discover and develop novel anti-AD agents.

Keywords: Alzheimer's disease, amyloid-beta, bisphosphonates, risedronate, alendronate, aggregation kinetics, transmission electron microscopy, molecular docking
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