LRRK2 and SNCA, the gene for α-synuclein, are the two of the most important genetic factors of Parkinson's disease (PD). A-synuclein is aggregated and accumulated in neurons and glia in PD and considered the pathogenic culprit of the disease. A-synuclein aggregates spread from a few discrete regions of the brain to larger areas as the disease progresses through cell-to-cell propagation mechanism. LRRK2 is involved in the regulation of vesicle trafficking, in particular in the endolysosomal and autophagic pathways. Studies also suggest that LRRK2 might regulate the pathogenic actions of α-synuclein. However, the relationship between these two proteins in the pathogenesis of PD remains elusive. Here, we review the current literature on the pathophysiological function of LRRK2 with an emphasis on its role in the endolysosomal and autophagic pathways. We also propose a potential mechanism by which LRRK2 is involved in the regulation of aggregation and the propagation of α-synuclein.

中文翻译：

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LRRK2-RAB轴调节小泡运输和α-突触核蛋白的繁殖。

LRRK2和SNCA是α-突触核蛋白的基因，是帕金森氏病（PD）的两个最重要的遗传因素。α-突触核蛋白在PD的神经元和神经胶质中聚集和积累，被认为是该病的病因。随着疾病通过细胞间传播机制发展，α-突触核蛋白聚集体从大脑的几个离散区域扩散到更大的区域。LRRK2参与小泡运输的调节，特别是在溶酶体和自噬途径中。研究还表明，LRRK2可能调节α-突触核蛋白的致病作用。但是，这两种蛋白在PD发病机理中的关系仍然难以捉摸。这里，我们回顾了有关LRRK2的病理生理功能的最新文献，重点是其在溶酶体和自噬途径中的作用。我们还提出了一种潜在的机制，LRRK2通过这种机制参与了α-突触核蛋白的聚集和增殖的调控。