Evaluation of sialic acid-analogs for the attenuation of amyloid-beta toxicity

Biochimica Et Biophysica Acta
Dhruva Dhavale, James E Henry

Abstract

Amyloid-beta peptide (Aβ) is the main constituent of senile plaques and is implicated in the pathogenesis of Alzheimer's disease (AD). To that end, agents which either sequester Aβ or interfere with Aβ interaction/binding to cells have been investigated as a means to reduce the pathological effects of Aβ. Different structural analogs of sialic acid (N-acetylneuramic acid) were used to decorate a chitosan backbone using EDC chemistry. FTIR and colorimetric assays were used to characterize the complexes. The ability of these complexes to attenuate Aβ toxicity was investigated in vitro using a model neuroblastoma cell line SH-SY5Y. Oxygen substitution in ring structure is responsible for the increase in toxicity and increase in protective properties of the complexes. Also, the multi OH tail present in sialic acid is critical to attenuate toxicity. Analogs show no protective properties which reinforces the conclusion that clustering of sugars in cellular membranes play a significant role in Aβ binding. Successfully produced compounds that showed varying degree of efficacy in attenuating Aβ toxicity to cells in culture. This work elucidates the impact that certain structures of sialic acid and its analogs can have on Aβ binding. It ...Continue Reading

References

Apr 15, 1997·European Journal of Biochemistry·J McLaurin, A Chakrabartty
Mar 21, 1998·The Journal of Biological Chemistry·J McLaurinA Chakrabartty
Mar 13, 2008·Journal of Lipid Research·Toshio ArigaRobert K Yu
Feb 2, 2010·Biochimica Et Biophysica Acta·Katsumi MatsuzakiKatsuhiko Yanagisawa

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Citations

Apr 20, 2021·Frontiers in Neuroscience·Punam Rawal, Liqin Zhao

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