Gene Therapy to Modulate Alpha-Synuclein in Synucleinopathies.
Gene Therapy to Modulate Alpha-Synuclein in Synucleinopathies.
复制标题
基因疗法在突触核蛋白病中调节α-突触核蛋白。
DOI：
10.3233/jpd-212679
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发表时间：
2021
期刊：
影响因子：
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通讯作者：
Manfredsson FP
中科院分区：
文献类型：
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作者：
Sandoval IM;Marmion DJ;Meyers KT;Manfredsson FP
α-突触核蛋白（α-Syn）是帕金森病（PD）病因学的关键因素，α-Syn的聚集、跨神经元扩散和/或缺失被认为是导致神经变性的分子过程中的关键事件。导致神经元死亡的病理发生的确切顺序在很大程度上仍然未知，并且很可能是多因素的。尽管未知，α-Syn的剂量和稳定性，自噬-溶酶体功能障碍，炎症，以及其他细胞损伤，都被描述为神经退行性过程中的参与事件。为此，在这篇综述中，我们讨论了基因治疗干预α-Syn介导的疾病的逻辑点，并回顾了基因治疗已经使用或可能在概念上使用的临床前工作体，以改善α-Syn诱导的神经毒性。我们讨论了传统意义上的基因治疗，即调节基因表达，以及使用病毒载体和纳米颗粒作为传递其他治疗方式的方法。
The protein alpha-Synuclein (α-Syn) is a key contributor to the etiology of Parkinson’s disease (PD) with aggregation, trans-neuronal spread, and/or depletion of α-Syn being viewed as crucial events in the molecular processes that result in neurodegeneration. The exact succession of pathological occurrences that lead to neuronal death are still largely unknown and are likely to be multifactorial in nature. Despite this unknown, α-Syn dose and stability, autophagy-lysosomal dysfunction, and inflammation, amongst other cellular impairments, have all been described as participatory events in the neurodegenerative process. To that end, in this review we discuss the logical points for gene therapy to intervene in α-Syn-mediated disease and review the preclinical body of work where gene therapy has been used, or could conceptually be used, to ameliorate α-Syn induced neurotoxicity. We discuss gene therapy in the traditional sense of modulating gene expression, as well as the use of viral vectors and nanoparticles as methods to deliver other therapeutic modalities.