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首页> 外文期刊>The European Journal of Neuroscience >Are PARKIN PARKIN patients ideal candidates for dopaminergic cell replacement therapies?
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Are PARKIN PARKIN patients ideal candidates for dopaminergic cell replacement therapies?

机译：Parkin Parkin患者是否是多巴胺能细胞更换疗法的理想候选人？

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Abstract Parkinson's is a heterogeneous, complex condition. Stratification of Parkinson's subtypes will be essential to identify those that will benefit most from a cell replacement therapy. Foetal mesencephalic grafts can alleviate motor symptoms in some Parkinson's patients. However, on‐going synucleinopathy results in the grafts eventually developing Lewy bodies, and they begin to fail. We propose that Parkinson's patients with PARKIN mutations may benefit most from a cell replacement therapy because (a) they often lack synucleinopathy, and (b) their neurodegeneration is often confined to the nigrostriatal pathway. While patients with PARKIN mutations exhibit clinical signs of Parkinson's, post‐mortem studies to date indicate the majority lack Lewy bodies suggesting the nigral dopaminergic neurons are lost in a cell autonomous manner independent of α‐synuclein mechanisms. Furthermore, these patients are usually younger, slow progressing and typically do not suffer from complex non‐nigral symptoms that are unlikely to be ameliorated by a cell replacement therapy. Transplantation of dopaminergic cells into the putamen of these patients will provide neurons with wild‐type PARKIN expression to re‐innervate the striatum. The focal nature of PARKIN‐mediated neurodegeneration and lack of active synucleinopathy in most young‐onset cases makes these patients ideal candidates for a dopaminergic cell replacement therapy. Strategies to improve the outcome of cell replacement therapies for sporadic Parkinson's include the use of adjunct therapeutics that target α‐synuclein spreading and the use of genetically engineered grafts that are resistant to synucleinopathy.
机译：摘要帕金森是一种异质，复杂的条件。帕金森亚型的分层对于鉴定来自细胞替代疗法的大部分受益的亚型至关重要。胎儿脑脑移植物可以缓解一些帕金森病人的电机症状。然而，正在进行的突触核苷病导致移植物最终开发乐理体，他们开始失败。我们建议帕金森患有Parkin突变的患者可能从细胞替代疗法中受益，因为（a）它们通常缺乏突触蛋白病，并且（b）它们的神经变性通常限制在纽粒状途径上。虽然Parkin突变患者表现出帕金森的临床症状，但迄今为止审查后的验尸研究表明，大多数缺乏石油群体，表明八胞长氨酰胺能神经元以α-突触核蛋白机制独立于细胞自主方式丧失。此外，这些患者通常更小，进展缓慢，并且通常不会受到细胞替代疗法不太可能改善复杂的非终峰症状。多巴胺能细胞移植到这些患者的腐败中，将提供具有野生型Parkin表达的神经元以重新支配纹状体。在大多数幼年患者中，Parkin介导的神经变性的局灶性和缺乏活性突触核病症使这些患者成为多巴胺能细胞替代治疗的理想候选者。改善零星帕金森的细胞替代疗法结果的策略包括使用靶向α-突触核蛋白的辅助治疗方法和使用对突触核苷病的转基因移植物的使用。

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