TY - JOUR
T1 - Spinal cord mRNA profile in patients with ALS
T2 - Comparison with transgenic mice expressing the human SOD-1 mutant
AU - Offen, Daniel
AU - Barhum, Yael
AU - Melamed, Eldad
AU - Embacher, Norbert
AU - Schindler, Christoph
AU - Ransmayr, Gerhard
N1 - Funding Information:
Acknowledgments The project was partially supported by the National Parkinson Foundation, Miami, FL, USA; the Norma and Alan Aufzein Chair for Research in Parkinson’s disease, Tel Aviv University, Israel; and the Scientific and Technical Cooperation Austria–Israel, project #III/7 1999.
PY - 2009/6
Y1 - 2009/6
N2 - 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.
AB - 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.
KW - Amyotrophic lateral sclerosis
KW - Apolipoprotein E
KW - Cathepsin
KW - EGFR
KW - Gene array
KW - LYST
KW - mRNA
UR - http://www.scopus.com/inward/record.url?scp=69249220446&partnerID=8YFLogxK
U2 - 10.1007/s12031-007-9004-z
DO - 10.1007/s12031-007-9004-z
M3 - מאמר
C2 - 18651250
AN - SCOPUS:69249220446
VL - 38
SP - 85
EP - 93
JO - Journal of Molecular Neuroscience
JF - Journal of Molecular Neuroscience
SN - 0895-8696
IS - 2
ER -