- 作者: Md Golam Sharoar, Arjun Thapa, Mohammad Shahnawaz, Vijay Sankar Ramasamy, Eun-Rhan Woo, Song Yub Shin and Il-Seon Park
- 作者服務機構: Department of Bio-materials Engineering, Chosun University, Gwanju, Republic of Korea
- 中文摘要: --
- 英文摘要:
Background: Aggregation of soluble, monomeric beta- amyloid (Abeta) to oligomeric and then insoluble fibrillar Abeta is a key pathogenic feature in development of Alzheimer's disease (AD). Increasing evidence suggests that toxicity is linked to diffusible Abeta oligomers, rather than to insoluble fibrils. The use of naturally occurring small molecules for inhibition of Abeta aggregation has recently attracted significant interest for development of effective therapeutic strategies against the disease. A natural polyphenolic flavone, Kaempferol-3-O-rhamnoside (K-3-rh), was utilized to investigate its effects on aggregation and cytotoxic effects of Abeta42 peptide. Several biochemical techniques were used to determine the conformational changes and cytotoxic effect of the peptide in the presence and absence of K-3-rh.
Results: K-3-rh showed a dose-dependent effect against Abeta42 mediated cytotoxicity. Anti-amyloidogenic properties of K-3-rh were found to be efficient in inhibiting fibrilogenesis and secondary structural transformation of the peptide. The consequence of these inhibitions was the accumulation of oligomeric structural species. The accumulated aggregates were smaller, soluble, non-beta-sheet and non-toxic aggregates, compared to preformed toxic Abeta oligomers. K-3-rh was also found to have the remodeling properties of preformed soluble oligomers and fibrils. Both of these conformers were found to remodel into non-toxic aggregates. The results showed that K-3-rh interacts with different Abeta conformers, which affects fibril formation, oligomeric maturation and fibrillar stabilization.
Conclusion: K-3-rh is an efficient molecule to hinder the self assembly and to abrogate the cytotoxic effects of Abeta42 peptide. Hence, K-3-rh and small molecules with similar structure might be considered for therapeutic development against AD. - 中文關鍵字: --
- 英文關鍵字: Aβ, Kaempferol-3-O-rhamnoside, Oligomer, Aggregation, Cytotoxicity, Alzheimer’s disease