%0 Journal Article
%T Keampferol-3-O-rhamnoside abrogates amyloid beta toxicity by modulating monomers and remodeling oligomers and fibrils to non-toxic aggregates
%A Sharoar Md
%A Thapa Arjun
%A Shahnawaz Mohammad
%A Ramasamy Vijay
%J Journal of Biomedical Science
%D 2012
%I BioMed Central
%R 10.1186/1423-0127-19-104
%X Background Aggregation of soluble, monomeric ¦Â- amyloid (A¦Â) to oligomeric and then insoluble fibrillar A¦Â is a key pathogenic feature in development of Alzheimer¡¯s disease (AD). Increasing evidence suggests that toxicity is linked to diffusible A¦Â oligomers, rather than to insoluble fibrils. The use of naturally occurring small molecules for inhibition of A¦Â 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 A¦Â42 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 A¦Â42 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-¦Â-sheet and non-toxic aggregates, compared to preformed toxic A¦Â 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 A¦Â 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 A¦Â42 peptide. Hence, K-3-rh and small molecules with similar structure might be considered for therapeutic development against AD.
%K A¦Â
%K Kaempferol-3-O-rhamnoside
%K Oligomer
%K Aggregation
%K Cytotoxicity
%K Alzheimer¡¯s disease
%U http://www.jbiomedsci.com/content/19/1/104