溶酶体离子通道蛋白在神经退行性疾病发生发展中的作用及机制研究

溶酶体离子通道蛋白异常引起溶酶体功能障碍是导致阿尔茨海默病(Alzheimer’s disease,AD)和帕金森病(Parkinson’s disease,PD)等神经退行性疾病的重要因素.溶酶体离子通道蛋白调节溶酶体内离子稳态、溶酶体膜电压以及溶酶体的酸度.溶酶体离子通道蛋白的结构或功能缺陷会引起溶酶体降解功能障碍,导致神经退行性疾病的发生发展.在这篇综述中,我们总结了各种离子通道蛋白调节溶酶体功能的过程及机制,以及离子通道蛋白异常参与神经退行性疾病的过程和机制.调节离子通道蛋白改善溶酶体的功能、促进异常聚集蛋白的清除,是神经退行性疾病治疗的潜在途径.

The Role and Underlying Mechanism of Lysosomal Ion Channels in The Pathogenesis of Neurodegenerative Diseases

Lysosomal dysfunction caused by abnormal lysosomal ion channels is an important factor leading to neurodegenerative diseases such as Alzheimer’s disease(AD)and Parkinson’s disease(PD).Lysosomes ion channels regulate lysosomal ion homeostasis,lysosomal membrane voltage,and lysosomal acidity.Structural or functional defects of lysosomal ion channels will cause lysosomal degradation dysfunction,leading to the occurrence and development of neurodegenerative diseases.In this review,The role and mechanisms of various lysosome ion channels in regulating lysosomal function were summarized.The underlying mechanism of the deficits of the ion channels in neurodegenerative diseases were also introduced.Regulating ion channels to improve lysosomal function and promote the clearance of abnormal aggregated proteins are underlying targets for the treatments of neurodegenerative diseases.