溶酶体pH稳态与帕金森病

Lysosomal pH Homeostasis and Parkinson’s Disease

溶酶体酸化功能障碍被认为是帕金森病的关键驱动因素。多种遗传因素通过损害溶酶体膜上的V-ATPase质子泵和离子通道功能影响溶酶体酸化。虽然溶酶体酸化影响帕金森病进展的潜在机制仍不清楚,但最近的研究表明,溶酶体酸化功能损伤早发于神经退行性病变和帕金森病病理晚期。本文通过对当前已经存在的溶酶体酸化和帕金森病细胞层面及小鼠体内表型的研究进行总结,从而提出恢复溶酶体pH可作为延缓帕金森病进展或治疗帕金森病的方案。

Lysosomal acidification dysfunction is considered to be a key driver of Parkinson’s disease. A variety of genetic factors affect lysosomal acidification by damaging the function of V-ATPase proton pump and ion channels on the lysosomal limiting membranes. Although the potential mechanism of lysosomal acidification affecting the progression of Parkinson’s disease is still unclear, recent studies have shown that lysosomal acidification damage occurs early in neurodegenerative lesions and late pathological stages of Parkinson’s disease. This paper summarizes the existing studies on lysosomal acidification and phenotypes of Parkinson’s disease over cellular level and mice, and proposes that the restoration of lysosomal pH can be used as a scheme to delay the progression of Parkinson’s disease or to rescue Parkinson’s disease.