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TitleThe Neglected Genes of ALS: Cytoskeletal Dynamics Impact Synaptic Degeneration in ALS.
Publication TypeJournal Article
Year of Publication2020
AuthorsCastellanos-Montiel, María José, Mathilde Chaineau, and Thomas M. Durcan
JournalFront Cell Neurosci
Volume14
Pagination594975
Date Published2020
ISSN1662-5102
Abstract

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that selectively affects motor neurons (MNs) of the cortex, brainstem, and spinal cord. Several genes have been linked to both familial (fALS) and sporadic (sALS) cases of ALS. Among all the ALS-related genes, a group of genes known to directly affect cytoskeletal dynamics (, , , , , , , , and ) is of high importance for MN health and survival, considering that MNs are large polarized cells with axons that can reach up to 1 m in length. In particular, cytoskeletal dynamics facilitate the transport of organelles and molecules across the long axonal distances within the cell, playing a key role in synapse maintenance. The majority of ALS-related genes affecting cytoskeletal dynamics were identified within the past two decades, making it a new area to explore for ALS. The purpose of this review is to provide insights into ALS-associated cytoskeletal genes and outline how recent studies have pointed towards novel pathways that might be impacted in ALS. Further studies making use of extensive analysis models to look for true hits, the newest technologies such as CRIPSR/Cas9, human induced pluripotent stem cells (iPSCs) and axon sequencing, as well as the development of more transgenic animal models could potentially help to: differentiate the variants that truly act as a primary cause of the disease from the ones that act as risk factors or disease modifiers, identify potential interactions between two or more ALS-related genes in disease onset and progression and increase our understanding of the molecular mechanisms leading to cytoskeletal defects. Altogether, this information will give us a hint on the real contribution of the cytoskeletal ALS-related genes during this lethal disease.

DOI10.3389/fncel.2020.594975
Alternate JournalFront Cell Neurosci
PubMed ID33281562
PubMed Central IDPMC7691654