Work

Mechanisms of Autophagy–Lysosome Dysfunction in Neurodegenerative Diseases

Year: 2024

Type: article

Abstract: Autophagy is a lysosome-based degradative process used to recycle obsolete cellular constituents and eliminate damaged organelles and aggregate-prone proteins. Their post-mitotic 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 aging on lysosomes and autophagy as a tipping point for late-age emergence of and related neurodegenerative disorders. Many of these diseases have primary defects in autophagy, e.g. 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

Source: Apollo (University of Cambridge)

DOI: 10.17863/cam.109551

Authors: Rubinsztein, David, Nixon, Ralph

Language: English

Topic: Autophagy in Disease and Therapy

Subfield: Epidemiology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: green