Parkinson's disease (PD) and frontotemporal dementia/amyotrophic lateral sclerosis (FTD/ALS) are insidious and incurable neurodegenerative diseases that represent a significant burden to affected individuals, caregivers, and an ageing population. Both PD and FTD/ALS are defined at post mortem by the presence of protein aggregates and the loss of specific subsets of neurons. We examine here the crucial role of lysosome dysfunction in these diseases and discuss recent evidence for converging mechanisms. This review draws upon multiple lines of evidence from genetic studies, human tissue, induced pluripotent stem cells (iPSCs), and animal models to argue that lysosomal failure is a primary mechanism of disease, rather than merely reflecting association with protein aggregate end-points. This review provides compelling rationale for targeting lysosomes in future therapeutics for both PD and FTD/ALS.

中文翻译：

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帕金森病和额颞叶痴呆/肌萎缩侧索硬化中心的溶酶体功能障碍

帕金森病 (PD) 和额颞叶痴呆/肌萎缩侧索硬化症 (FTD/ALS) 是隐匿且无法治愈的神经退行性疾病，对受影响的个人、护理人员和老龄化人口构成重大负担。PD 和 FTD/ALS 都是在死后通过蛋白质聚集体的存在和特定神经元子集的丢失来定义的。我们在这里检查溶酶体功能障碍在这些疾病中的关键作用，并讨论最近的趋同机制的证据。这篇综述利用来自基因研究、人体组织、诱导多能干细胞 (iPSC) 和动物模型的多条证据来论证溶酶体衰竭是疾病的主要机制，而不仅仅是反映与蛋白质聚集终点的关联。