武汉大学张振涛研究团队发现，病理性α-突触核蛋白从肾脏传播到大脑可能促成帕金森病的发生。相关论文于2025年1月23日在线发表于国际学术期刊《自然—神经科学》。

研究人员表示，路易小体病（LBD）的发病机制，包括帕金森病（PD），涉及α-突触核蛋白（α-Syn）聚集，起始于外周器官并传播到大脑。慢性肾衰竭患者中PD的发病率较高，但其潜在机制仍不清楚。

研究人员观察到LBD患者的肾脏中存在α-Syn沉积，并且在晚期肾病患者中，肾脏和中枢神经系统也发现了α-Syn沉积，尽管这些患者没有记录的LBD。研究人员在雄性小鼠中发现，肾脏从血液中去除α-Syn，肾功能衰竭时这一过程减少，导致α-Syn在肾脏中的沉积，随后扩散到大脑。肾脏内注射α-Syn纤维可诱导α-Syn病理从肾脏传播到大脑，而肾脏去神经化则能阻止这一过程。删除血液细胞中的α-Syn能缓解α-Syn A53T转基因小鼠的病理。

因此，肾脏可能作为致病性α-Syn传播的起始点，而肾功能受损可能促成LBD的发生。

附：英文原文

Title: Propagation of pathologic α-synuclein from kidney to brain may contribute to Parkinson’s disease

Author: Yuan, Xin, Nie, Shuke, Yang, Yingxu, Liu, Congcong, Xia, Danhao, Meng, Lanxia, Xia, Yue, Su, Hua, Zhang, Chun, Bu, Lihong, Deng, Min, Ye, Keqiang, Xiong, Jing, Chen, Liam, Zhang, Zhentao

Issue&Volume: 2025-01-23

Abstract: The pathogenesis of Lewy body diseases (LBDs), including Parkinson’s disease (PD), involves α-synuclein (α-Syn) aggregation that originates in peripheral organs and spreads to the brain. PD incidence is increased in individuals with chronic renal failure, but the underlying mechanisms remain unknown. Here we observed α-Syn deposits in the kidneys of patients with LBDs and in the kidney and central nervous system of individuals with end-stage renal disease without documented LBDs. In male mice, we found that the kidney removes α-Syn from the blood, which is reduced in renal failure, causing α-Syn deposition in the kidney and subsequent spread into the brain. Intrarenal injection of α-Syn fibrils induces the propagation of α-Syn pathology from the kidney to the brain, which is blocked by renal denervation. Deletion of α-Syn in blood cells alleviates pathology in α-Syn A53T transgenic mice. Thus, the kidney may act as an initiation site for pathogenic α-Syn spread, and compromised renal function may contribute to the onset of LBDs.

DOI: 10.1038/s41593-024-01866-2

Source: https://www.nature.com/articles/s41593-024-01866-2