Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2009-4-9
pubmed:abstractText
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder of the motor neurons in the spinal cord, brainstem, and motor cortex. Ten percent of ALS cases are familial, with both autosomal dominant and recessive modes of inheritance reported. Mutations in the copper/zinc superoxide-dismutase-1 (SOD-1) gene, the first gene linked with ALS, result in the classical ALS phenotype. To date, 135 mutations have been identified in the SOD-1 gene, accounting for approximately 20% of familial ALS cases. Mutations are widely distributed throughout the gene with preponderance for exon 4 and 5. Although mutations result in a toxic gain of function of the SOD-1 enzyme, which normally functions as a free radical scavenger, the mechanisms underlying motor neuron degeneration have not been clearly elucidated. Evidence is emerging of a complex interaction between genetic and molecular factors, with resultant damage of critical target proteins and organelles within the motor neuron. The clinical effectiveness afforded by anti-glutamatergic agents such as riluzole, suggests that glutamate excitotoxicity contributes to neurodegeneration in ALS, with glutamate excitotoxicity mediated via corticomotoneurons that provide a direct link between the motor cortex and the spinal motor neuron. This review provides an overview of the genetics of ALS, and describes recent advances in the understanding of the pathophysiological mechanisms underlying neurodegeneration.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Ciliary Neurotrophic Factor, http://linkedlifedata.com/resource/pubmed/chemical/Glutamic Acid, http://linkedlifedata.com/resource/pubmed/chemical/Intermediate Filament Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Membrane Glycoproteins, http://linkedlifedata.com/resource/pubmed/chemical/Nerve Tissue Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Neurofilament Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Ribonuclease, Pancreatic, http://linkedlifedata.com/resource/pubmed/chemical/Sodium-Potassium-Exchanging ATPase, http://linkedlifedata.com/resource/pubmed/chemical/Superoxide Dismutase, http://linkedlifedata.com/resource/pubmed/chemical/Survival of Motor Neuron 1 Protein, http://linkedlifedata.com/resource/pubmed/chemical/Vascular Endothelial Growth Factor A, http://linkedlifedata.com/resource/pubmed/chemical/angiogenin, http://linkedlifedata.com/resource/pubmed/chemical/peripherin, http://linkedlifedata.com/resource/pubmed/chemical/superoxide dismutase 1
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1566-5240
pubmed:author
pubmed:issnType
Print
pubmed:volume
9
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
255-72
pubmed:dateRevised
2011-7-19
pubmed:meshHeading
pubmed-meshheading:19355908-Amyotrophic Lateral Sclerosis, pubmed-meshheading:19355908-Animals, pubmed-meshheading:19355908-Ciliary Neurotrophic Factor, pubmed-meshheading:19355908-Glutamic Acid, pubmed-meshheading:19355908-Humans, pubmed-meshheading:19355908-Intermediate Filament Proteins, pubmed-meshheading:19355908-Membrane Glycoproteins, pubmed-meshheading:19355908-Mitochondria, pubmed-meshheading:19355908-Motor Neurons, pubmed-meshheading:19355908-Mutation, pubmed-meshheading:19355908-Nerve Degeneration, pubmed-meshheading:19355908-Nerve Tissue Proteins, pubmed-meshheading:19355908-Neurofilament Proteins, pubmed-meshheading:19355908-Ribonuclease, Pancreatic, pubmed-meshheading:19355908-Sodium-Potassium-Exchanging ATPase, pubmed-meshheading:19355908-Superoxide Dismutase, pubmed-meshheading:19355908-Survival of Motor Neuron 1 Protein, pubmed-meshheading:19355908-Vascular Endothelial Growth Factor A
pubmed:year
2009
pubmed:articleTitle
Pathophysiology of neurodegeneration in familial amyotrophic lateral sclerosis.
pubmed:affiliation
Prince of Wales Medical Research Institute and Prince of Wales Clinical School, University of New South Wales, Sydney, Australia.
pubmed:publicationType
Journal Article, Review, Research Support, Non-U.S. Gov't