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 (ALS2, DCTN1, PFN1, KIF5A, NF-L, NF-H, PRPH, SPAST, and TUBA4A) 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.
Highlights
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the progressive loss of motor neurons (MNs) within the brain cortex, brainstem, and spinal cord
The purpose of this review is to provide insight into several ALS-related genes linked to the disruption of cytoskeletal dynamics
The discovery of ALS-related genes that affect cytoskeletal dynamics is very recent and their study in an ALS-related context does not extend more than 20 years
Summary
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the progressive loss of motor neurons (MNs) within the brain cortex, brainstem, and spinal cord. About 90–95% of ALS cases are sporadic (sALS) while the remaining 5–10% are familial (fALS) (Brown and Al-Chalabi, 2017; Volk et al, 2018). The clinical presentation of ALS is heterogeneous and sometimes it can be misdiagnosed with other MN diseases. Some sALS cases cannot be attributed to genetic or biologic factors instead they are ascribed to environmental and undefined factors (Brown and Al-Chalabi, 2017). Many ALS patients show cognitive and behavioral changes characteristic of frontotemporal dementia (FTD), a neurodegenerative disease that shares neuropathological and genetic features with ALS. It has been suggested that both FTD and ALS are a continuum of the same phenotypic spectrum (Lipton et al, 2004; Vance et al, 2006; Volk et al, 2018)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
