Anti-amyloidogenic effect of AA3E2 attenuates beta-amyloid induced toxicity in SK-N-MC cells
SCIE
SCOPUS
- Title
- Anti-amyloidogenic effect of AA3E2 attenuates beta-amyloid induced toxicity in SK-N-MC cells
- Authors
- Shaykhalishahi, Hamed; Taghizadeh, Mohammad; Yazdanparast, Razieh; Chang, Young-Tae
- Date Issued
- 2010-06
- Publisher
- ELSEVIER IRELAND LTD
- Abstract
- beta-Amyloid peptide (A beta) is believed to play a recognized role in pathogenesis of Alzheimer's disease (AD). Self-association of A beta peptide into amyloid fibrils causes neurotoxicity. Compounds capable of interfering with A beta-A beta interaction through binding to nucleation sites can inhibit A beta amyloidogenesis and A beta-induced cytotoxicity. AA3E2 is a triazine-derivative whose anti-amyloidogenic ability has previously been established. In the present study, we evaluated the protective effect of AA3E3 against A beta(1-42)-induced toxicity in SK-N-MC cell line. The cell exposure to the co-incubated A beta(1-42) with AA3E2 decreased the cell viability loss dose-dependently, compared to cells exposed to A beta(1-42) fibrils. Co-incubation with AA3E2 also attenuated the ROS production, activation of caspase-3 and the extent of apoptotic cell death induced by A beta(1-42) fibril. Moreover, the 3D structure of the molecular associates between A beta(1-42) and AA3E2 were theoretically determined by docking studies. Our docking data indicated that AA3E2 inhibits the formation of AS fibril likely via binding to the nucleation site within the hydrophobic region of A beta (KLVFF). These observations provide the background for future design of more elegant beta-breaking agents for dissolution of A beta fibrillar aggregates. (C) 2010 Elsevier Ireland Ltd. All rights reserved.
- Keywords
- ALZHEIMERS-DISEASE; OXIDATIVE STRESS; A-BETA; HYDROGEN-PEROXIDE; FIBRIL FORMATION; PRECURSOR PROTEIN; GAMMA-SECRETASE; PEPTIDE; AGGREGATION; INVOLVEMENT
- URI
- https://oasis.postech.ac.kr/handle/2014.oak/50221
- DOI
- 10.1016/j.cbi.2010.03.042
- ISSN
- 0009-2797
- Article Type
- Article
- Citation
- CHEMICO-BIOLOGICAL INTERACTIONS, vol. 186, no. 1, page. 16 - 23, 2010-06
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