Ghobeh M.,University of Tehran |
Ahmadian S.,University of Tehran |
Meratan A.A.,Agricultural and Natural Resources University of Ramin |
Ebrahim-Habibi A.,Tehran University of Medical Sciences |
And 3 more authors.
Biopolymers - Peptide Science Section | Year: 2014
The 25-35 fragment of the amyloid β (Aβ) peptide is a naturally occurring proteolytic by-product that retains the pathophysiology of its larger parent molecule, whose deposition has been shown to involve mitochondrial dysfunction. Hence, disruption of Aβ(25-35) aggregates could afford an effective remedial strategy for Alzheimer's disease (AD). In the present study, the effect of a number of selected small-molecule natural products (polyphenols: resveratrol, quercetin, biochanin A, and indoles: indole- 3-acetic acid, indole-3-carbinol (I3C)) on Aβ(25-35) fibrillogenesis was explored under physiological conditions, and interaction of the resulting structures with rat brain mitochondria was investigated. Several techniques, including fluorescence, circular dichroism, and transmission electron microscopy were utilized to characterize the aggregation products, and possible mitochondrial membrane permeabilization was determined following release of marker enzymes. Results demonstrate the capacity of Aβ(25-35) fibrils to damage mitochondria and suggest how small molecules may afford protection. While I3C appeared more effective in inhibiting the fibrillation process, all natural products behaved similarly in destabilizing preformed aggregates. It is concluded that elucidation of such protection may provide important insights into the development of preventive and therapeutic agents for AD. © 2014 Wiley Periodicals, Inc.