Laboratory of Neurochemistry and Cell Biology, Department of Biochemistry and Biophysics, Institute of Health Sciences, Federal University of Bahia, Salvador, Bahia, 40110-100, Brazil.
Molecular & Clinical Pharmacology, ICBM, Faculty of Medicine, University of Chile, Independencia, 1027, Santiago, Chile.
Neurotox Res. 2020 Oct;38(3):579-584. doi: 10.1007/s12640-020-00237-6. Epub 2020 Jun 25.
Flavonoids have been suggested to protect dopaminergic neurons in Parkinson's disease based on studies that used exogenous neurotoxins. In this study, we tested the protective ability of agathisflavone in SH-SY5Y cells exposed to the endogenous neurotoxin aminochrome. The ability of aminochrome to induce loss of lysosome acidity is an important mechanism of its neurotoxicity. We demonstrated that the flavonoid inhibited cellular death and lysosomal dysfunction induced by aminochrome. In addition, we demonstrated that the protective effect of agathisflavone was suppressed by antagonists of estrogen receptors (ERα and ERβ). These results suggest lysosomal protection and estrogen signaling as mechanisms involved in agathisflavone neuroprotection in a Parkinson's disease study model.
类黄酮已被认为可以基于使用外源性神经毒素的研究来保护帕金森病中的多巴胺能神经元。在这项研究中,我们测试了 agathisflavone 在暴露于内源性神经毒素氨基chrome 的 SH-SY5Y 细胞中的保护能力。氨基chrome 诱导溶酶体酸度丧失的能力是其神经毒性的重要机制。我们证明了该黄酮类化合物抑制了氨基chrome 诱导的细胞死亡和溶酶体功能障碍。此外,我们还证明了 agathisflavone 的保护作用被雌激素受体(ERα 和 ERβ)拮抗剂所抑制。这些结果表明溶酶体保护和雌激素信号转导是 agathisflavone 在帕金森病研究模型中发挥神经保护作用的机制。