Abstract
Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are considered to be part of a disease spectrum that is associated with causative mutations and risk variants in a wide range of genes. Mounting evidence indicates that several of these genes are linked to the endolysosomal system, highlighting the importance of this pathway in ALS/FTD. Although many studies have focused on how disruption of this pathway impacts on autophagy, recent findings reveal that this may not be the whole picture: specifically, disrupting autophagy may not be sufficient to induce disease, whereas disrupting the endolysosomal system could represent a crucial pathogenic driver. In this review we discuss the connections between ALS/FTD and the endolysosomal system, including a breakdown of how disease-associated genes are implicated in this pathway. We also explore the potential downstream consequences of disrupting endolysosomal activity in the brain, outside of an effect on autophagy.
Original language | English (US) |
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Pages (from-to) | 1025-1041 |
Number of pages | 17 |
Journal | Trends in neurosciences |
Volume | 46 |
Issue number | 12 |
DOIs | |
State | Published - Dec 2023 |
Keywords
- C9ORF72
- TDP-43
- TMEM106B
- autophagy
- neurodegeneration
- proteinopathy
ASJC Scopus subject areas
- General Neuroscience