Sir Martin Evans Building, School of Biosciences, Cardiff University, Museum Avenue, Cardiff, CF10 3AX, United Kingdom.
Sir Martin Evans Building, School of Biosciences, Cardiff University, Museum Avenue, Cardiff, CF10 3AX, United Kingdom.
Ageing Res Rev. 2016 Dec;32:104-121. doi: 10.1016/j.arr.2016.07.005. Epub 2016 Aug 8.
Lysosomal storage diseases and diseases of ageing share many features both at the physiological level and with respect to the mechanisms that underlie disease pathogenesis. Although the exact pathophysiology is not exactly the same, it is astounding how many similar pathways are altered in all of these diseases. The aim of this review is to provide a summary of the shared disease mechanisms, outlining the similarities and differences and how genetics, insight into rare diseases and functional research has changed our perspective on the causes underlying common diseases of ageing. The lysosome should no longer be considered as just the stomach of the cell or as a suicide bag, it has an emerging role in cellular signalling, nutrient sensing and recycling. The lysosome is of fundamental importance in the pathophysiology of diseases of ageing and by comparing against the LSDs we not only identify common pathways but also therapeutic targets so that ultimately more effective treatments can be developed for all neurodegenerative diseases.
溶酶体贮积症和衰老相关疾病在生理水平和疾病发病机制的基础机制方面具有许多共同特征。尽管确切的病理生理学并不完全相同,但令人惊讶的是,所有这些疾病中都有多少相似的途径发生了改变。本综述的目的是总结共同的疾病机制,概述相似之处和不同之处,以及遗传学、对罕见疾病的深入了解和功能研究如何改变我们对衰老相关常见疾病根本原因的看法。溶酶体不应再被视为细胞的“胃”或“自杀袋”,它在细胞信号转导、营养感应和回收中具有新兴作用。溶酶体在衰老相关疾病的病理生理学中具有重要意义,通过与 LSD 进行比较,我们不仅可以确定共同的途径,还可以确定治疗靶点,从而最终为所有神经退行性疾病开发更有效的治疗方法。