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The Ginkgo biloba Extract EGb 761 Modulates Proteasome Activity and Polyglutamine Protein Aggregation

机译:银杏叶提取物银杏叶提取物761调节蛋白酶体活性和聚谷氨酰胺蛋白聚集。

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摘要

The standardized Ginkgo biloba extract EGb 761 has well-described antioxidative activities and effects on different cytoprotective signaling pathways. Consequently, a potential use of EGb 761 in neurodegenerative diseases has been proposed. A common characteristic feature of a variety of such disorders is the pathologic formation of protein aggregates, suggesting a crucial role for protein homeostasis. In this study, we show that EGb 761 increased the catalytic activity of the proteasome and enhanced protein degradation in cultured cells. We further investigated this effect in a cellular model of Huntington's disease (HD) by employing cells expressing pathologic variants of a polyglutamine protein (polyQ protein). We show that EGb 761 affected these cells by (i) increasing proteasome activity and (ii) inducing a more efficient degradation of aggregation-prone proteins. These results demonstrate a novel activity of EGb 761 on protein aggregates by enhancing proteasomal protein degradation, suggesting a therapeutic use in neurodegenerative disorders with a disturbed protein homeostasis.
机译:标准化的银杏叶提取物银杏叶提取物761具有良好描述的抗氧化活性,并且对不同的细胞保护信号通路具有影响。因此,已经提出了EGb 761在神经退行性疾病中的潜在用途。各种此类疾病的共同特征是蛋白质聚集体的病理形成,这提示了蛋白质稳态的关键作用。在这项研究中,我们表明EGb 761增加了蛋白酶体的催化活性并增强了培养细胞中的蛋白质降解。我们通过采用表达聚谷氨酰胺蛋白(polyQ蛋白)病理变异的细胞,进一步研究了亨廷顿舞蹈病(HD)细胞模型中的这种作用。我们显示,EGB 761通过(i)增加蛋白酶体活性和(ii)诱导易于聚集的蛋白质降解而影响了这些细胞。这些结果证明了EGB 761通过增强蛋白酶体蛋白质降解而对蛋白质聚集体具有新的活性,表明其在具有蛋白质稳态的紊乱的神经退行性疾病中的治疗用途。

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