Abstract
The aetiology of sporadic amyotrophic lateral sclerosis (ALS), a fatal paralytic disease, is largely unknown. Here we show that there is a defect in the editing of the messenger RNA encoding the GluR2 subunit of glutamate AMPA receptors in the spinal motor neurons of individuals affected by ALS. This failure to swap an arginine for a glutamine residue at a crucial site in the subunit, which occurs normally in the affected brain areas of patients with other neurodegenerative diseases, will interfere with the correct functioning of the glutamate receptors and may be a contributory cause of neuronal death in ALS patients.
MeSH terms
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Amyotrophic Lateral Sclerosis / genetics*
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Amyotrophic Lateral Sclerosis / metabolism
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Amyotrophic Lateral Sclerosis / pathology*
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Arginine / genetics
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Arginine / metabolism
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Cell Death
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Codon / genetics
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Glutamine / genetics
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Glutamine / metabolism
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Humans
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Motor Neurons / metabolism*
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Motor Neurons / pathology*
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Purkinje Cells / metabolism
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Purkinje Cells / pathology
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RNA Editing / genetics*
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Receptors, AMPA / chemistry
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Receptors, AMPA / genetics*
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Receptors, AMPA / metabolism*
Substances
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Codon
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RNA, Messenger
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Receptors, AMPA
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Glutamine
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Arginine
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glutamate receptor ionotropic, AMPA 2