Autophagy is a lysosome-based degradative process used to recycle obsolete cellular constituents and eliminate damaged organelles and aggregate-prone proteins. Their postmitotic nature and extremely polarized morphologies make neurons particularly vulnerable to disruptions caused by autophagy–lysosomal defects, especially as the brain ages. Consequently, mutations in genes regulating autophagy and lysosomal functions cause a wide range of neurodegenerative diseases. Here, we review the role of autophagy and lysosomes in neurodegenerative diseases such as Alzheimer disease, Parkinson disease and frontotemporal dementia. We also consider the strong impact of cellular ageing on lysosomes and autophagy as a tipping point for the late-age emergence of related neurodegenerative disorders. Many of these diseases have primary defects in autophagy, for example affecting autophagosome formation, and in lysosomal functions, especially pH regulation and calcium homeostasis. We have aimed to provide an integrative framework for understanding the central importance of autophagic–lysosomal function in neuronal health and disease.

自噬是一种基于溶酶体的降解过程，用于回收过时的细胞成分并消除受损的细胞器和易聚集蛋白质。它们的有丝分裂后性质和极化形态使神经元特别容易受到自噬-溶酶体缺陷引起的破坏，尤其是随着大脑年龄的增长。因此，调节自噬和溶酶体功能的基因突变会导致广泛的神经退行性疾病。在这里，我们回顾了自噬和溶酶体在神经退行性疾病中的作用，如阿尔茨海默病、帕金森病和额颞叶痴呆。我们还认为细胞衰老对溶酶体和自噬的强烈影响是相关神经退行性疾病晚期出现的转折点。其中许多疾病在自噬方面具有原发性缺陷，例如影响自噬体形成，以及溶酶体功能，尤其是 pH 调节和钙稳态。我们旨在提供一个综合框架，用于理解自噬-溶酶体功能在神经元健康和疾病中的核心重要性。