Multiple roles for the cytoskeleton in ALS

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease caused by more than sixty genes identified through classic linkage analysis and new sequencing methods. Yet no clear mechanism of onset, cure, or effective treatment is known. Popular discourse classifies the proteins encoded from ALS-related genes into four disrupted processes: proteostasis, mitochondrial function and ROS, nucleic acid regulation, and cytoskeletal dynamics. Surprisingly, the mechanisms detailing the contribution of the neuronal cytoskeletal in ALS are the least explored, despite involvement in these cell processes. Eight genes directly regulate properties of cytoskeleton function and are essential for the health and survival of motor neurons, including: TUBA4A, SPAST, KIF5A, DCTN1, NF, PRPH, ALS2, and PFN1. Here we review the properties and studies exploring the contribution of each of these genes to ALS.

Automated summary

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease caused by multiple genes, but the clear mechanism and effective treatment is still unknown. The contribution of neuronal cytoskeleton in ALS is the least explored among the disrupted processes. This article reviews the properties and studies of 8 genes that directly regulate cytoskeleton function and their contribution to ALS.