Evaluation of heptelidic acid as a potential inhibitor for tau aggregation-induced Alzheimer's disease and associated neurotoxicity.

Published on May 7, 2021in International Journal of Biological Macromolecules5.162
· DOI :10.1016/J.IJBIOMAC.2021.05.018
Lei Zhang , Zhuo Wang + 2 AuthorsMojtaba Falahati24
Estimated H-index: 24
(IAU: Islamic Azad University)
Abstract Tau is a major component of protein plaques in tauopathies, especially Alzheimer's disease (AD). The purpose of the present study is to explore the inhibitory effects of heptelidic acid as a bioactive compound from fungus T. koningii on tau fibrillization and associated neurotoxicity. The influences of various concentrations of heptelidic acid on tau fibrillization and underlying neurotoxicity were explored by assessment of the biophysical (ThT/Nile red fluorescence, CR absorbance, CD, and TEM analysis) and cellular (MTT, LDH, and caspase-3) assays. It was shown that heptelidic acid inhibited tau fibrillization in a concentration-dependent manner and the highest inhibition was determined at the ratio of 1:2 mol of heptelidic acid: tau. On the other hand, cellular assays indicated that the viability, LDH release, and caspase-3 activity were regulated when neurons were exposed to tau samples co-incubated with heptelidic acid. In conclusion, it may be indicated that heptelidic acid inhibited tau fibrillization which was accompanied by formation of amorphous aggregated species of tau with much less neurotoxicity than tau amyloid alone. Thus, heptelidic acid can be considered as a potential candidate in preventive care studies to inhibit the formation of tau plaques as neurotoxic species.
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