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Interaction of Aβ(25–35) fibrillation products with mitochondria: Effect of small‐molecule natural products
Author(s) -
Ghobeh Maryam,
Ahmadian Shahin,
Meratan Ali Akbar,
EbrahimHabibi Azadeh,
Ghasemi Atiyeh,
Shafizadeh Mahshid,
NematGorgani Mohsen
Publication year - 2014
Publication title -
peptide science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.556
H-Index - 125
eISSN - 1097-0282
pISSN - 0006-3525
DOI - 10.1002/bip.22572
Subject(s) - chemistry , small molecule , biochanin a , mitochondrion , indole test , resveratrol , biochemistry , circular dichroism , fibril , fibrillogenesis , peptide , biophysics , molecule , organic chemistry , medicine , daidzein , genistein , biology
ABTRACT 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. Biopolymers (Pept Sci) 102: 473–486, 2014.