ALS: Recent Developments from Genetics Studies

Abstract

Amyotrophic lateral sclerosis (ALS) is a fatal disorder that is characterized by a progressive degeneration of the upper and lower motor neurons. Most cases appear to be sporadic, but 5-10 % of cases have a family history of the disease. High-throughput DNA sequencing and related genomic capture tools are methodological advances which have rapidly contributed to an acceleration in the discovery of genetic risk factors for both familial and sporadic ALS. It is interesting to note that as the number of ALS genes grows, many of the proteins they encode are in shared intracellular processes. This review will summarize some of the recent advances and gene discovery made in ALS.

CNS inflammation and neurodegeneration

“…Superoxide dismutase (SOD) binds free superoxide radicals for conversion into molecular oxygen and hydrogen peroxide, the latter of which is then broken down by catalase (101). Over 160 mutations in the SOD gene have been found in forms of ALS (102,103).…”

Amyotrophic Lateral Sclerosis

“…genes have now been reproducibly implicated in familial ALS, sporadic ALS, or both. [18][19][20] A by-product of the genetic studies that is highly relevant to therapeutic development has been the generation of mouse models of ALS. Strikingly, transgenic expression of mutant SOD1 protein 21 and, more recently, profilin 1 (PFN1) 22 generates a neurodegenerative, paralytic process in mice that mimics many aspects of human ALS.…”

Genetic Correction of SOD1 Mutant iPSCs Reveals ERK and JNK Activated AP1 as a Driver of Neurodegeneration in Amyotrophic Lateral Sclerosis

“…Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative condition characterized by a progressive loss of upper and lower MNs (Therrien et al., 2016). There is no cure to halt or reverse the degeneration and the median patient survival is 3–5 years (Robberecht and Philips, 2013).…”