Differential expression of molecular motors in the motor cortex of sporadic ALS.
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.
Pantelidou
Maria
M
Department of Biological Sciences, University of Cyprus and Cyprus Institute of Neurology and Genetics, P.O. Box 20537, 1678 Nicosia, Cyprus.
Zographos
Spyros E
SE
Lederer
Carsten W
CW
Kyriakides
Theodore
T
Pfaffl
Michael W
MW
Santama
Niovi
N
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
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