School of Public Health Sciences, University of Waterloo, Waterloo, ON N2L 3G1, Canada.
Int J Mol Sci. 2022 Jul 22;23(15):8060. doi: 10.3390/ijms23158060.
The present paper investigated the association of Parkinson's disease etiology with phosphate toxicity, a pathophysiological condition in which dysregulated phosphate metabolism causes excessive inorganic phosphate sequestration in body tissue that damages organ systems. Excessive phosphate is proposed to reduce Complex I function of the mitochondrial electron transport chain in Parkinson's disease and is linked to opening of the mitochondrial permeability transition pore, resulting in increased reactive oxygen species, inflammation, DNA damage, mitochondrial membrane depolarization, and ATP depletion causing cell death. Parkinson's disease is associated with α-synuclein and Lewy body dementia, a secondary tauopathy related to hyperphosphorylation of tau protein, and tauopathy is among several pathophysiological pathways shared between Parkinson's disease and diabetes. Excessive phosphate is also associated with ectopic calcification, bone mineral disorders, and low levels of serum vitamin D in patients with Parkinson's disease. Sarcopenia and cancer in Parkinson's disease patients are also associated with phosphate toxicity. Additionally, Parkinson's disease benefits are related to low dietary phosphate intake. More studies are needed to investigate the potential mediating role of phosphate toxicity in the etiology of Parkinson's disease.
本文探讨了帕金森病病因与磷酸盐毒性之间的关联。磷酸盐毒性是一种病理生理状态，其中失调的磷酸盐代谢导致过多的无机磷酸盐在体内组织中蓄积，从而损害器官系统。过量的磷酸盐被认为会降低帕金森病中线粒体电子传递链复合物 I 的功能，并与线粒体通透性转换孔的打开有关，导致活性氧增加、炎症、DNA 损伤、线粒体膜去极化和 ATP 耗竭，从而导致细胞死亡。帕金森病与α-突触核蛋白和路易体痴呆有关，后者是一种与 tau 蛋白过度磷酸化相关的继发性 tau 病，tau 病是帕金森病和糖尿病之间共享的几种病理生理途径之一。过量的磷酸盐还与帕金森病患者的异位钙化、骨矿物质紊乱和血清维生素 D 水平低有关。帕金森病患者的肌肉减少症和癌症也与磷酸盐毒性有关。此外，帕金森病的益处与低饮食磷酸盐摄入有关。需要更多的研究来探讨磷酸盐毒性在帕金森病病因中的潜在介导作用。
