title: Pathogenesis of amyotrophic lateral sclerosis.
abstract: Amyotrophic lateral sclerosis (ALS) or motor neuron disease is a rapidly progressive neurodegenerative disorder. The primary involvement is of motor neurons in the brain, spinal cord and peripherally. There is secondary weakness of muscles and primary involvement of other brain regions, especially involving cognition.
  
  
  
  Peer-reviewed journal articles and reviews. PubMed.gov
  
  
  
  The pathogenesis of ALS remains largely unknown. There are a wide range of potential mechanisms related to neurodegeneration. An increasing number of genetic factors are recognized.
  
  
  
  There remains controversy, or lack of knowledge, in explaining how cellular events manifest as the complex human disease. There is controversy as to how well cellular and animal models of disease relate to the human disease.
  
  
  
  Large-scale international collaborative genetic epidemiological studies are replacing local studies. Therapies related to pathogenesis remain elusive, with the greatest advances to date relating to provision of care (including multidisciplinary management) and supportive care (nutrition and respiratory support).
  
  
  
  The identification of C9orf72 hexanucleotide repeats as the most frequent genetic background to ALS, and the association with frontotemporal dementia, gives the potential of a genetic background against which to study other risk factors, triggers and pathogenic mechanisms, and to develop potential therapies.
authors.affiliation: Department of Molecular Neuroscience, UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK.
authors.forename: Sarah
authors.initials: S
authors.lastname: Morgan
authors.affiliation: Department of Clinical Neuroscience, UCL Institute of Neurology, Rowland Hill Street, London NW3 2PF, UK r.orrell@ucl.ac.uk.
authors.forename: Richard W
authors.initials: RW
authors.lastname: Orrell
mesh_terms: D017668:Age of Onset; D000690:Amyotrophic Lateral Sclerosis / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology*; D000927:Anticonvulsants / Q000627:therapeutic use; D000073885:C9orf72 Protein; D004268:DNA-Binding Proteins; D056344:Executive Function / Q000187:drug effects; D055106:Genome-Wide Association Study; D006801:Humans; D058990:Molecular Targeted Therapy / Q000639:trends*; D009154:Mutation / Q000235:genetics; D011506:Proteins; D034702:RNA-Binding Protein FUS; D019782:Riluzole / Q000627:therapeutic use; D000072105:Superoxide Dismutase-1
chemical_list: D000927:Anticonvulsants; D000073885:C9orf72 Protein; C568651:C9orf72 protein, human; D004268:DNA-Binding Proteins; C000599550:FUS protein, human; D011506:Proteins; D034702:RNA-Binding Protein FUS; C000606290:SOD1 protein, human; C000598624:TARDBP protein, human; D019782:Riluzole; D000072105:Superoxide Dismutase-1
keywords: amyotrophic lateral sclerosis; genetics; pathogenesis; treatment