Zhang Lei, Wang Zhuo, Yuan Xueling, Sui Rubo, Falahati Mojtaba
School of Nursing, Jinzhou Medical University, Jinzhou 121099, China.
Department of Neurology, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou 121099, China.
Int J Biol Macromol. 2021 Jul 31;183:1155-1161. doi: 10.1016/j.ijbiomac.2021.05.018. Epub 2021 May 7.
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) and cellular (MTT, LDH, and caspase-3) assays. It was shown that heptelidic acid inhibited tau fibrillization in a concentration-dependent manner. 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.
Tau蛋白是tau蛋白病（尤其是阿尔茨海默病，即AD）中蛋白斑块的主要成分。本研究的目的是探索来自康宁木霉的生物活性化合物庚二酸对tau蛋白纤维化及相关神经毒性的抑制作用。通过生物物理分析（硫代黄素T/尼罗红荧光、刚果红吸光度、圆二色光谱和透射电子显微镜）和细胞分析（MTT法、乳酸脱氢酶释放法和半胱天冬酶-3活性检测），研究了不同浓度庚二酸对tau蛋白纤维化及潜在神经毒性的影响。结果表明，庚二酸以浓度依赖性方式抑制tau蛋白纤维化。另一方面，细胞分析表明，当神经元暴露于与庚二酸共同孵育的tau蛋白样品时，细胞活力、乳酸脱氢酶释放和半胱天冬酶-3活性受到调节。总之，可能表明庚二酸抑制了tau蛋白纤维化，同时伴随着tau蛋白无定形聚集物的形成，其神经毒性远低于单独的tau蛋白淀粉样纤维。因此，庚二酸可被视为预防保健研究中抑制作为神经毒性物质的tau蛋白斑块形成的潜在候选物。
