Amyotrophic lateral sclerosis (ALS) is a difficult disease to study as it is mostly sporadic and rapidly progressive. Identification of genes causing familial ALS (FALS) has been instrumental in advancing our understanding of ALS pathogenesis, most notably with the use of mutant superoxide dismutase 1 (SOD1) models of disease. For 15 years SOD1 models have been the backbone of ALS research, but no effective treatments have been developed. However, recent advances have been made in the genetics of ALS with the identification of mutations in TAR DNA binding protein (TDP-43) and fused in sarcoma/translocated in liposarcoma (FUS), both of which have roles in RNA-processing and gene expression. Molecular links between ALS and frontotemporal dementia (FTD) are also suggested by linkage of ALS-FTD to chromosome 9. The study of the genetics of sporadic ALS (SALS) has been less fruitful, although this may change as we enter the era of resequencing. Further important clues as to the causes of ALS will come from the identification of other gene mutations that cause FALS, variants that increase susceptibility to SALS, and genetic factors that modify the ALS phenotype.
Keywords: Amyotrophic Lateral Sclerosis, Genetics, TDP-43, FUS
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