title: Advances in treating amyotrophic lateral sclerosis: insights from pathophysiological studies.
abstract: Amyotrophic lateral sclerosis (ALS) is the most frequently occurring of the neuromuscular degenerative disorders, with a median survival time of 3-5 years. The pathophysiological mechanisms underlying ALS are multifactorial, with a complex interaction between genetic factors and molecular pathways. To date 16 genes and loci have been associated with ALS, with mutations in DNA/RNA-regulating genes including the recently described c9orf72 (chromosome 9 open reading frame 72) gene, suggesting an important role for dysregulation of RNA metabolism in ALS pathogenesis. Further, dysfunction of molecular pathways, including glutamate-mediated excitotoxicity, has been identified in sporadic and familial ALS, indicating the existence of a common pathogenic pathway. These pathophysiological insights have suggested novel therapeutic approaches, including stem cell and genetics-based strategies, providing hope for feasible treatment of ALS.
authors.affiliation: Westmead Clinical School, University of Sydney, Sydney, Australia; Neurosciences Research Australia, Sydney, Australia. Electronic address: s.vucic@neura.edu.au.
authors.forename: Steve
authors.initials: S
authors.lastname: Vucic
authors.affiliation: Brain Science Institute, Robert Packard Center for Amyotrophic Lateral Sclerosis Research, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Rothstein
authors.affiliation: Neurosciences Research Australia, Sydney, Australia; Brain and Mind Research Institute, University of Sydney, Sydney, Australia.
authors.forename: Matthew C
authors.initials: MC
authors.lastname: Kiernan
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics / Q000473:pathology / Q000503:physiopathology* / Q000628:therapy*; D000073885:C9orf72 Protein; D015984:Causality; D004268:DNA-Binding Proteins / Q000235:genetics; D006801:Humans; D018696:Neuroprotective Agents / Q000627:therapeutic use; D011506:Proteins / Q000235:genetics
chemical_list: D000073885:C9orf72 Protein; C568651:C9orf72 protein, human; D004268:DNA-Binding Proteins; D018696:Neuroprotective Agents; D011506:Proteins