title: Differential expression of molecular motors in the motor cortex of sporadic ALS.
abstract: The molecular mechanisms underlying the selective neurodegeneration of motor neurons in amyotrophic lateral sclerosis (ALS) are inadequately understood. Recent breakthroughs have implicated impaired axonal transport, mediated by molecular motors, as a key element for disease onset and progression. The current work identifies the expression of 15 kinesin-like motors in healthy human motor cortex, including three novel isoforms. Our comprehensive quantitative mRNA analysis in control and sporadic ALS (SALS) motor cortex specimens detects SALS-specific down-regulation of KIF1Bbeta and novel KIF3Abeta, two isoforms we show to be enriched in the brain, and also of SOD1, a key enzyme linked to familial ALS. This is accompanied by a marked reduction of KIF3Abeta protein levels. In the motor cortex KIF3Abeta localizes in cholinergic neurons, including upper motor neurons. No mutations causing splicing defects or altering protein-coding sequences were identified in the genes of the three proteins. The present study implicates two motor proteins as possible candidates in SALS pathology.
authors.affiliation: Department of Biological Sciences, University of Cyprus and Cyprus Institute of Neurology and Genetics, P.O. Box 20537, 1678 Nicosia, Cyprus.
authors.forename: Maria
authors.initials: M
authors.lastname: Pantelidou
authors.forename: Spyros E
authors.initials: SE
authors.lastname: Zographos
authors.forename: Carsten W
authors.initials: CW
authors.lastname: Lederer
authors.forename: Theodore
authors.initials: T
authors.lastname: Kyriakides
authors.forename: Michael W
authors.initials: MW
authors.lastname: Pfaffl
authors.forename: Niovi
authors.initials: N
authors.lastname: Santama
mesh_terms: D000368:Aged; D017398:Alternative Splicing / Q000235:genetics; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D000818:Animals; D002799:Cholinergic Fibers / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D005819:Genetic Markers / Q000235:genetics; D006801:Humans; D016547:Kinesins / Q000235:genetics; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008875:Middle Aged; D020409:Molecular Motor Proteins / Q000235:genetics / Q000378:metabolism*; D009044:Motor Cortex / Q000378:metabolism* / Q000503:physiopathology; D009046:Motor Neurons / Q000378:metabolism* / Q000473:pathology; D009154:Mutation / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics; D020033:Protein Isoforms / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D013482:Superoxide Dismutase / Q000235:genetics; D000072105:Superoxide Dismutase-1
chemical_list: D005819:Genetic Markers; C091053:KIF1B protein, human; C087415:KIF3A protein, human; D020409:Molecular Motor Proteins; D009419:Nerve Tissue Proteins; D020033:Protein Isoforms; D012333:RNA, Messenger; C000606290:SOD1 protein, human; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D016547:Kinesins