Molecular signature of late-stage human ALS revealed by expression profiling of postmortem spinal cord gray matter

Fernando Dangond, Daehee Hwang, Sandra Camelo, Piera Pasinelli, Matthew P. Frosch, Gregory Stephanopoulos, George Stephanopoulos, Robert H. Brown, Steven R. Gullans

Research output: Contribution to journalArticle

113 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)229-239
Number of pages11
JournalPhysiological genomics
Volume16
DOIs
StatePublished - Apr 2004

Keywords

  • Amyotrophic lateral sclerosis
  • Apoptosis
  • DNA microarrays
  • Excitotoxicity
  • Mitochondria

ASJC Scopus subject areas

  • Physiology
  • Genetics

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    Dangond, F., Hwang, D., Camelo, S., Pasinelli, P., Frosch, M. P., Stephanopoulos, G., Stephanopoulos, G., Brown, R. H., & Gullans, S. R. (2004). Molecular signature of late-stage human ALS revealed by expression profiling of postmortem spinal cord gray matter. Physiological genomics, 16, 229-239. https://doi.org/10.1152/physiolgenomics.00087.2001