| RESEARCH ARTICLE |
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| Year : 2012 | Volume
: 1
| Issue : 1 | Page : 27-40 |
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Amyloidogenic proteins, in their fibrillar states, may be detrimental via different mechanisms: Perspective of potential curative/preventive strategies against neurodegenerative disorders
Reza Khodarahmi1, Zahra Hossein-pour2, Kamran Mansouri2, Seyyed Abolghasem Ghadami2
1 Medical Biology Research Center, Kermanshah University of Medical Sciences; Department of Pharmacognosy and Biotechnology, Faculty of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, Iran
2 Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran
Correspondence Address:
Reza Khodarahmi
Medical Biology Research Center, Kermanshah University of Medical Sciences; Department of Pharmacognosy and Biotechnology, Faculty of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah
Iran
 Source of Support: None, Conflict of Interest: None  | Check |
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The aberrant assembly of proteins into fibrillar aggregates is accused to be the primary cause of pathogenesis of neurodegenerative diseases. But the structural determinants of protein fibrils that are responsible for cell dysfunction are not yet clear. In the current study, cell culture, spectroscopic techniques as well as theoretical and structural investigations were used to determine the ability of different fibrillar aggregates to impair cell viability. We evaluated two types of amyloid fibrils that efficiently impair cell viability when added to cell culture. Theoretical and structural investigations indicated differences in the hydrophobic characteristics of protein molecules in the fibrils, so that our findings suggest that surface hydrophobicity may be considered as a main determinant of fibrillar assemblies to cause cellular dysfunction and its consequences such as neurodegeneration. Also, the main objective of the present study was to discuss the potential role of peroxidase activity of “heme-amyloid fibril” complex in neurodegenerative disorders onset/progression using the protein-based experimental models. The results of the present study also suggest that oxidative stress may be involved in neurodegenerative cell toxicity via several independent (mechanistic) routes. The data on origin of amyloid-mediated cell dysfunction may help us to postpone/attenuate the onset/extent of irreversible part of neurodegenerative pathogenesis.
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