title: Amyotrophic lateral sclerosis is a multifactorial disease.
abstract: Amyotrophic lateral sclerosis (ALS) is probably biphasic. An initial trigger(s) is followed by a terminal cascade coinciding with the onset of neurological deficits. The terminal cascade involves interactive multifactorial pathogenic mechanisms. Aging must play a crucial role leading to multiple defective or degraded gene products accumulating with progressing years. This in turn leads to failure of receptor integrity and resulting excitotoxicity, free radical accumulation, failure of neurotrophism, and possibly immunological disturbances. These events are predated by months or years by a trigger which is also likely to be multifactorial and cumulative. Evidence suggests that environmental factors may be important triggers. Failure of specific glutamate transporters and calcium binding proteins may account for selective vulnerability of the corticomotoneuronal system. It is postulated that in ALS the primary target cell is the corticomotoneuron or the local circuit interneurons which modulate its activity. Glia cells may play an important role in the demise of the corticomotoneuronal cell. The disordered corticomotoneuron induces excessive excitatory transmitter (glutamate?) release at the corticomotoneuronal-spinal-motoneuronal synapse resulting in the subsequent demise of this neuron.
authors.affiliation: Neuromuscular Diseases Unit, Vancouver General Hospital, British Columbia, Canada.
authors.forename: A
authors.initials: A
authors.lastname: Eisen
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000209:etiology / Q000235:genetics / Q000503:physiopathology*; D000818:Animals; D002874:Chromosome Mapping; D002891:Chromosomes, Human, Pair 21; D018698:Glutamic Acid / Q000502:physiology / Q000633:toxicity; D006801:Humans; D009154:Mutation; D009414:Nerve Growth Factors / Q000096:biosynthesis / Q000235:genetics / Q000627:therapeutic use; D016900:Neurofilament Proteins / Q000235:genetics; D009498:Neurotoxins / Q000633:toxicity; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics / Q000502:physiology; D015290:Second Messenger Systems; D015398:Signal Transduction; D013045:Species Specificity; D013482:Superoxide Dismutase / Q000235:genetics
chemical_list: D009414:Nerve Growth Factors; D016900:Neurofilament Proteins; D009498:Neurotoxins; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D013482:Superoxide Dismutase