The endolysosomal pathway and ALS/FTD

Trends Neurosci. 2023 Oct 10:S0166-2236(23)00222-9. doi: 10.1016/j.tins.2023.09.004. Online ahead of print.ABSTRACTAmyotrophic 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.PMID:37827960 | DOI:10.1016/j.tins.2023.09.004
Source: Trends in Neurosciences - Category: Neuroscience Authors: Source Type: research