Differential expression of molecular motors in the motor cortex of sporadic ALS

Neurobiology of Disease

Maria Pantelidou¹  Niovi Santama¹  Carsten W. Lederer¹  Spyros E. Zographos¹  Michael W. Pfaffl²  Theodore Kyriakides³ 

[1] Department of Biological Sciences, University of Cyprus and Cyprus Institute of Neurology and Genetics, P.O. Box 20537, 1678 Nicosia, Cyprus;Physiology-Weihenstephan, Center of Life and Food Sciences, Technical University of Munich, Germany;The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus;

关键词: Real-time RT-PCR;    Motor neuron disease;    Kinesin-like proteins;    KIF3A;    KIF1Bβ;   

DOI  :  

来源: DOAJ

【 摘 要 】

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 KIF1Bβ and novel KIF3Aβ, 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 KIF3Aβ protein levels. In the motor cortex KIF3Aβ 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.

【 授权许可】

Unknown