College of Medicine, Department of Neurological Sciences, University of Nebraska Medical Center, Omaha, NE, USA.
Sci Rep. 2024 Oct 11;14(1):23861. doi: 10.1038/s41598-024-74775-w.
Parkinson's disease (PD) is the most common progressive neurodegenerative movement disorder and results from the selective loss of dopaminergic neurons in the substantia nigra pars compacta. Pink1 and Parkin are proteins that function together in mitochondrial quality control, and when they carry loss-of-function mutations lead to familial forms of PD. While much research has focused on central nervous system alterations in PD, peripheral contributions to PD pathogenesis are increasingly appreciated. We report Pink1/Parkin regulate glycolytic and mitochondrial oxidative metabolism in peripheral blood mononuclear cells (PBMCs) from rats. Pink1/Parkin deficiency induces changes in the circulating lymphocyte populations, namely increased CD4 + T cells and decreased CD8 + T cells and B cells. Loss of Pink1/Parkin leads to elevated platelet counts in the blood and increased platelet-T cell aggregation. Platelet-lymphocyte aggregates are associated with increased thrombosis risk suggesting targeting the Pink1/Parkin pathway in the periphery might have therapeutic potential.
帕金森病（PD）是最常见的进行性神经退行性运动障碍，是由黑质致密部多巴胺能神经元的选择性丧失引起的。Pink1 和 Parkin 是两种在线粒体质量控制中共同发挥作用的蛋白质，当它们携带功能丧失突变时，会导致家族性 PD。虽然许多研究都集中在 PD 中枢神经系统的改变上，但人们越来越认识到外周对 PD 发病机制的贡献。我们报告 Pink1/Parkin 调节大鼠外周血单个核细胞（PBMCs）中的糖酵解和线粒体氧化代谢。Pink1/Parkin 缺乏会诱导循环淋巴细胞群的变化，即增加 CD4+T 细胞和减少 CD8+T 细胞和 B 细胞。Pink1/Parkin 的缺失会导致血液中血小板计数升高，血小板-T 细胞聚集增加。血小板-淋巴细胞聚集与血栓形成风险增加有关，这表明靶向外周的 Pink1/Parkin 途径可能具有治疗潜力。
