帕金森病 z-bio 2025-02-13 430

　　The alpha synuclein released by red blood cells aggregates in the kidneys and spreads to the brain, promoting the occurrence of Parkinson's disease　　

　　With the support of National Natural Science Foundation projects (approval numbers: 82271447, 81771382, 82301430), Professor Zhang Zhentao's research team at Wuhan University has made progress in the study of the pathogenesis of Parkinson's disease. The research results, titled "Propagation of pathological alpha synuclein from kidney to brain may contribute to Parkinson's disease", were published online on January 23, 2025 in the journal Nature Neuroscience. Paper link: https://www.nature.com/articles/s41593-024-01866-2 .

　　Parkinson's disease (PD) is the second most common neurodegenerative disease, characterized by motor symptoms such as resting tremors, muscle rigidity, and bradykinesia, as well as non motor symptoms such as olfactory, sleep, and cognitive impairments. The prevalence rate of the elderly over 65 years old in China is 1.7%. With the aggravation of population aging, its incidence rate is increasing year by year. The characteristic pathological changes of PD are degeneration and loss of dopaminergic neurons in the substantia nigra pars compacta, resulting in the formation of pathological inclusion bodies within the remaining neurons. The main component of these bodies is abnormally aggregated alpha synuclein (alpha Synuclein, alpha Syn). After the formation of alpha Syn aggregates, they propagate along the neural pathway, inducing more alpha Syn aggregation in new neurons, leading to continuous expansion of the lesion. Therefore, the formation of α - Syn aggregates is the core link in the pathogenesis of PD, and the origin site of α - Syn aggregates is an important scientific issue in the field of PD research. The traditional view is that alpha Syn aggregates originate in the brain, but recent studies have found that half of PD patients' lesions originate from peripheral organs and then spread into the brain, known as "somatic PD". However, it is still unclear where the alpha Syn aggregates in these patients originate from.

　　The research team systematically examined the peripheral organs of PD patients and found a large number of alpha Syn aggregates in the kidneys. Renal dysfunction is an independent risk factor for PD, and some patients with renal failure also have alpha Syn aggregates in their kidneys and nervous system. Further research has found that α - Syn in the blood is mainly metabolized by the kidneys. When renal dysfunction occurs, the clearance ability of α - Syn is blocked, and it deposits in the kidneys to form aggregates. Inducing renal failure in PD mouse models can significantly accelerate alpha Syn aggregation and nerve damage. Directly injecting alpha Syn aggregates into the kidneys not only induces the formation of alpha Syn aggregates in the kidneys, but also allows them to propagate along neural pathways into the brain. Cutting off the neural innervation of the kidneys can block the spread of lesions into the brain. So where does the deposition of alpha Syn in the kidneys come from? The research team found that red blood cells contain a large amount of alpha Syn, with a concentration about 1000 times higher than that in cerebrospinal fluid. The normal lifespan of red blood cells is 3 months. When renal dysfunction occurs, the free alpha Syn produced by red blood cell fragmentation cannot be degraded by the kidneys and will accumulate in the kidneys and spread to the brain, leading to the occurrence of Parkinson's disease. Specific knockout of α - Syn in blood cells of PD model mice can significantly delay the progression of lesions (Figure).

　　This study found that the kidney is an important peripheral organ for the origin of alpha Syn aggregates, which not only deepens our understanding of the origin of PD lesions, but also suggests that clearing peripheral alpha Syn can delay the progression of PD, providing new ideas for the treatment of PD.