In Parkinson's disease (PD), as in many other neurodegenerative disorders, mitochondrial dysfunction, protein misfolding, and proteotoxic stress underly the disease process. For decades, the primary symptomatic treatment for PD has been the dopamine precursor L-DOPA (Levodopa). L-DOPA however can initiate protein misfolding through its ability to mimic the protein amino acid L-tyrosine, resulting in random errors in aminoacylation and L-DOPA becoming mistakenly inserted into the polypeptide chain of proteins in place of L-tyrosine.

In the present study we examined the impact that the generation of DOPA-containing proteins had on human neuroblastoma cell (SH-SY5Y) function in vitro. We showed that even in the presence of antioxidants there was a significant accumulation of cytosolic ubiquitin in DOPA-treated cells, an upregulation in the endosomal-lysosomal degradation system, deleterious changes to mitochondrial morphology and a marked decline in mitochondrial function.The effects of L-DOPA on mitochondrial function were not observed with D-DOPA, the stereoisomer of L-DOPA that cannot be inserted into proteins so did not result from oxidative stress. We could fully protect against these effects by co-treatment with L-tyrosine, supporting the view that misincorporation of L-DOPA into proteins contributed to these cytotoxic effects, leading us to suggest that co-treatment with L-tyrosine could be beneficial therapeutically.

与许多其他神经退行性疾病一样，在帕金森氏病（PD）中，线粒体功能障碍，蛋白质错误折叠和蛋白毒性应激是该疾病的潜在原因。数十年来，PD的主要症状治疗方法是多巴胺前体L-DOPA（左旋多巴）。然而，L-DOPA可以通过其模拟蛋白质氨基酸L-酪氨酸的能力来引发蛋白质错误折叠，从而导致氨酰化中的随机错误，并且L-DOPA代替L-酪氨酸被错误地插入蛋白质的多肽链中。

在本研究中，我们研究了含DOPA的蛋白质的产生对体外人神经母细胞瘤细胞（SH-SY5Y）功能的影响。我们发现即使在存在抗氧化剂的情况下，DOPA处理的细胞中也会有大量的细胞溶质泛素积累，内体-溶酶体降解系统上调，线粒体形态的有害变化以及线粒体功能的显着下降。 D-DOPA未观察到-DOPA对线粒体功能的作用，D-DOPA是L-DOPA的立体异构体，无法插入蛋白质中，因此不是由氧化应激引起的。通过与L-酪氨酸共同处理，我们可以完全防止这些作用，支持以下观点：L-DOPA误掺入蛋白质会导致这些细胞毒性作用，从而使我们提出与L-酪氨酸共同处理可能有益于治疗。