Pathogenic commonalities between spinal muscular atrophy and amyotrophic lateral sclerosis: Converging roads to therapeutic development

European Journal of Medical Genetics
Mélissa BowermanCédric Raoul

Abstract

Spinal muscular atrophy (SMA) and amyotrophic lateral sclerosis (ALS) are the two most common motoneuron disorders, which share typical pathological hallmarks while remaining genetically distinct. Indeed, SMA is caused by deletions or mutations in the survival motor neuron 1 (SMN1) gene whilst ALS, albeit being mostly sporadic, can also be caused by mutations within genes, including superoxide dismutase 1 (SOD1), Fused in Sarcoma (FUS), TAR DNA-binding protein 43 (TDP-43) and chromosome 9 open reading frame 72 (C9ORF72). However, it has come to light that these two diseases may be more interlinked than previously thought. Indeed, it has recently been found that FUS directly interacts with an Smn-containing complex, mutant SOD1 perturbs Smn localization, Smn depletion aggravates disease progression of ALS mice, overexpression of SMN in ALS mice significantly improves their phenotype and lifespan, and duplications of SMN1 have been linked to sporadic ALS. Beyond genetic interactions, accumulating evidence further suggests that both diseases share common pathological identities such as intrinsic muscle defects, neuroinflammation, immune organ dysfunction, metabolic perturbations, defects in neuron excitability and selective motone...Continue Reading

Citations

Apr 21, 2018·Pharmaceutical Patent Analyst·Hermann Am Mucke
Oct 2, 2020·International Journal of Molecular Sciences·Fang LuoXin Wang
Jan 4, 2021·Annals of Neurology·Matthieu MoisseUNKNOWN Project MinE Sequencing Consortium
Mar 2, 2021·Biochimica Et Biophysica Acta. Molecular Cell Research·Vidhya BharathiBasant K Patel
Jun 3, 2021·International Journal of Molecular Sciences·Marc-Olivier DeguiseRashmi Kothary

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