title: [Aberration of the spliceosome in amyotrophic lateral sclerosis].
abstract: TDP-43 is a nuclear protein that plays a role in RNA metabolism, and its dysfunction has been implicated in the pathogenesis of amyotrophic lateral sclerosis (ALS), a typical adult-onset motor neuron disease. We investigated RNA metabolism in relation to TDP-43 function in neuronal tissues affected by ALS, and found a decrease in the number of nuclear GEM bodies, as well as reduced expression of minor spliceosomes, which are functional RNA-protein complexes. Similar features have been reported in spinal muscular atrophy (SMA), a motor neuron disease affecting infants. These findings, together with those reported in SMA, strongly suggest that reduction of minor spliceosomes has an important role in the pathomechanism underlying the selective degeneration of motor neurons characteristic of both ALS and SMA.
authors.affiliation: Department of Neurology, Brain Research Institute, Niigata University.
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Ishihara
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Kakita
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Takahashi
authors.forename: Osamu
authors.initials: O
authors.lastname: Onodera
authors.forename: Masatoyo
authors.initials: M
authors.lastname: Nishizawa
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics*; D000818:Animals; D002869:Chromosome Aberrations; D004268:DNA-Binding Proteins / Q000502:physiology; D006801:Humans; D012313:RNA / Q000378:metabolism; D014897:Spinal Muscular Atrophies of Childhood / Q000235:genetics; D017381:Spliceosomes / Q000235:genetics* / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; C000598624:TARDBP protein, human; D012313:RNA