Alpha-lipoic acid exhibits anti-amyloidogenicity for beta-amyloid fibrils in vitro.
Alpha-lipoic acid exhibits anti-amyloidogenicity for beta-amyloid fibrils in vitro.
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DOI：
10.1016/j.bbrc.2006.01.063
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发表时间：
2006-03
影响因子：
3.1
通讯作者：
K. Ono;M. Hirohata;M. Yamada
中科院分区：
文献类型：
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作者：
K. Ono;M. Hirohata;M. Yamada
抑制β-淀粉样蛋白原纤维（fAβ）的形成以及使CNS中预先形成的fAβ不稳定将是治疗阿尔茨海默病（AD）的有吸引力的治疗靶点。利用硫磺素T荧光光谱分析和电子显微镜研究，我们研究了α-硫辛酸（LA）及其代谢产物二氢硫辛酸（DHLA）在体外37°C、pH 7.5条件下对fAβ形成、延伸和去稳定化的影响。LA和DHLA剂量依赖性地抑制淀粉样β蛋白形成fAβ，以及它们的延伸。此外，它们使预先形成的fAβ不稳定。LA和DHLA可能是开发AD治疗药物的关键分子。
Inhibition of the formation of β-amyloid fibrils (fAβ), as well as the destabilization of preformed fAβ in the CNS would be attractive therapeutic targets for the treatment of Alzheimer’s disease (AD). Using fluorescence spectroscopic analysis with thioflavin T and electron microscopic studies, we examined the effects of α-lipoic acid (LA) and the metabolic product of LA, dihydrolipoic acid (DHLA), on the formation, extension, and destabilization of fAβ at pH 7.5 at 37°C in vitro. LA and DHLA dose-dependently inhibited fAβ formation from amyloid β-protein, as well as their extension. Moreover, they destabilized preformed fAβs. LA and DHLA could be key molecules for the development of therapeutics for AD.