Spinal cord mRNA profile in patients with ALS: comparison with transgenic mice expressing the human SOD-1 mutant.
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by loss of motor neurons in the cerebral cortex, brain stem, and spinal cord. Most cases (90%) are classified as sporadic ALS (sALS). The remainder 10% are inherited and referred to as familial ALS, and 2% of instances are due to mutations in Cu/Zn superoxide dismutase (SOD1). Using cDNA microarray on postmortem spinal cord specimens of four sALS patients compared to four age-matched nonneurological controls, we found major changes in the expression of mRNA in 60 genes including increase of cathepsin B and cathepsin D (by the factors 2 and 2.3, respectively), apolipoprotein E (Apo E; factor 4.2), epidermal growth factor receptor (factor 10), ferritin (factor 2), and lysosomal trafficking regulator (factor 10). The increase in the expression of these genes was verified by quantitative reverse transcriptase polymerase chain reaction. Further analysis of these genes in hSOD1-G93A transgenic mice revealed increase in the expression in parallel with the deterioration of motor functions quantified by means of rotorod performance. The comparability of the findings in sALS patients and in the hSOD1-G93A transgenic mouse model suggests that the examined genes may play a specific role in the pathogenesis of ALS.
Offen
Daniel
D
Felsenstein Medical Research Center, Department of Neurology, Rabin Medical Center, Sackler School of Medicine, Tel Aviv University, Petah-Tikva, 49100, Israel. doffen@post.tau.ac.il
Barhum
Yael
Y
Melamed
Eldad
E
Embacher
Norbert
N
Schindler
Christoph
C
Ransmayr
Gerhard
G
D000368:Aged; D000369:Aged, 80 and over; D000690:Amyotrophic Lateral Sclerosis / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D000818:Animals; D002401:Cathepsin B / Q000235:genetics / Q000378:metabolism; D002402:Cathepsin D / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism; D005260:Female; D005293:Ferritins / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008875:Middle Aged; D008969:Molecular Sequence Data; D020411:Oligonucleotide Array Sequence Analysis; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D013116:Spinal Cord / Q000166:cytology / Q000201:enzymology / Q000502:physiology; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D000072105:Superoxide Dismutase-1; D033921:Vesicular Transport Proteins
D047908:Intracellular Signaling Peptides and Proteins; C491133:Lyst protein, mouse; D011506:Proteins; D012333:RNA, Messenger; C000606290:SOD1 protein, human; D033921:Vesicular Transport Proteins; D005293:Ferritins; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D066246:ErbB Receptors; D002401:Cathepsin B; D002402:Cathepsin D