TY - JOUR
T1 - Molecular signature of late-stage human ALS revealed by expression profiling of postmortem spinal cord gray matter
AU - Dangond, Fernando
AU - Hwang, Daehee
AU - Camelo, Sandra
AU - Pasinelli, Piera
AU - Frosch, Matthew P.
AU - Stephanopoulos, Gregory
AU - Stephanopoulos, George
AU - Brown, Robert H.
AU - Gullans, Steven R.
PY - 2004/4
Y1 - 2004/4
N2 - Little is known about global gene expression patterns in the human neurodegenerative disease amyotrophic lateral sclerosis (ALS). To address this, we used high-density oligonucleotide microarray technology to compare expression levels of ∼6,800 genes in postmortem spinal cord gray matter obtained from individuals with ALS as well as normal individuals. Using Fisher discriminant analysis (FDA) and leave-one-out cross-validation (LOOCV), we discerned an ALS-specific signature. Moreover, it was possible to distinguish familial ALS (FALS) from sporadic ALS (SALS) gene expression profiles. Characterization of the specific genes significantly altered in ALS uncovered a pro-inflammatory terminal state. Moreover, we found alterations in genes involved in mitochondrial function, oxidative stress, excitotoxicity, apoptosis, cytoskeletal architecture, RNA transcription and translation, proteasomal function, and growth and signaling. It is apparent from this study that DNA microarray analysis and appropriate bioinformatics can reveal distinct phenotypic changes that underlie the terminal stages of neurodegeneration in ALS.
AB - Little is known about global gene expression patterns in the human neurodegenerative disease amyotrophic lateral sclerosis (ALS). To address this, we used high-density oligonucleotide microarray technology to compare expression levels of ∼6,800 genes in postmortem spinal cord gray matter obtained from individuals with ALS as well as normal individuals. Using Fisher discriminant analysis (FDA) and leave-one-out cross-validation (LOOCV), we discerned an ALS-specific signature. Moreover, it was possible to distinguish familial ALS (FALS) from sporadic ALS (SALS) gene expression profiles. Characterization of the specific genes significantly altered in ALS uncovered a pro-inflammatory terminal state. Moreover, we found alterations in genes involved in mitochondrial function, oxidative stress, excitotoxicity, apoptosis, cytoskeletal architecture, RNA transcription and translation, proteasomal function, and growth and signaling. It is apparent from this study that DNA microarray analysis and appropriate bioinformatics can reveal distinct phenotypic changes that underlie the terminal stages of neurodegeneration in ALS.
KW - Amyotrophic lateral sclerosis
KW - Apoptosis
KW - DNA microarrays
KW - Excitotoxicity
KW - Mitochondria
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U2 - 10.1152/physiolgenomics.00087.2001
DO - 10.1152/physiolgenomics.00087.2001
M3 - Article
C2 - 14645737
AN - SCOPUS:1442282943
SN - 1531-2267
VL - 16
SP - 229
EP - 239
JO - Physiological genomics
JF - Physiological genomics
ER -