title: Sporadic and hereditary amyotrophic lateral sclerosis (ALS).
abstract: Genetic discoveries in ALS have a significant impact on deciphering molecular mechanisms of motor neuron degeneration. The identification of SOD1 as the first genetic cause of ALS led to the engineering of the SOD1 mouse, the backbone of ALS research, and set the stage for future genetic breakthroughs. In addition, careful analysis of ALS pathology added valuable pieces to the ALS puzzle. From this joint effort, major pathogenic pathways emerged. Whereas the study of TDP43, FUS and C9ORF72 pointed to the possible involvement of RNA biology in motor neuron survival, recent work on P62 and UBQLN2 refocused research on protein degradation pathways. Despite all these efforts, the etiology of most cases of sporadic ALS remains elusive. Newly acquired genomic tools now allow the identification of genetic and epigenetic factors that can either increase ALS risk or modulate disease phenotype. These developments will certainly allow for better disease modeling to identify novel therapeutic targets for ALS. This article is part of a Special Issue entitled: Neuromuscular Diseases: Pathology and Molecular Pathogenesis.
authors.affiliation: Division of Neuromuscular Medicine, The Ken and Ruth Davee Department of Neurology and Clinical Neurosciences, Feinberg School of Medicine Northwestern University, Chicago, IL 60611, USA. Electronic address: s-ajroud@northwestern.edu.
authors.forename: Senda
authors.initials: S
authors.lastname: Ajroud-Driss
authors.affiliation: Division of Neuromuscular Medicine, The Ken and Ruth Davee Department of Neurology and Clinical Neurosciences, Feinberg School of Medicine Northwestern University, Chicago, IL 60611, USA; Department of Cell and Molecular Biology, Feinberg School of Medicine Northwestern University, Chicago, IL, USA.
authors.forename: Teepu
authors.initials: T
authors.lastname: Siddique
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport / Q000235:genetics / Q000378:metabolism; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000818:Animals; D000071183:Autophagy-Related Proteins; D000073885:C9orf72 Protein; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D002470:Cell Survival; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D044127:Epigenesis, Genetic; D030342:Genetic Diseases, Inborn / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D006801:Humans; D051379:Mice; D009046:Motor Neurons / Q000378:metabolism / Q000473:pathology; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D034702:RNA-Binding Protein FUS / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D000072105:Superoxide Dismutase-1; D014452:Ubiquitins / Q000235:genetics / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D000071183:Autophagy-Related Proteins; D000073885:C9orf72 Protein; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D011506:Proteins; D034702:RNA-Binding Protein FUS; D016601:RNA-Binding Proteins; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D014452:Ubiquitins; C568651:C9orf72 protein, human; C000599550:FUS protein, human; C000599551:FUS protein, mouse; C118585:P62 protein, human; C000606290:SOD1 protein, human; C000598624:TARDBP protein, human; C578077:Tardbp protein, mouse; C405662:UBQLN2 protein, human; C538988:UBQLN2 protein, mouse; C000606291:Sod1 protein, mouse
keywords: Familial ALS; Paradigm shift; Pathogenesis; Sporadic ALS