Molecular signature of late-stage human ALS revealed by expression profiling of postmortem spinal cord gray matter.
Publication/Presentation Date
1-15-2004
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 approximately 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.
Volume
16
Issue
2
First Page
229
Last Page
239
ISSN
1531-2267
Published In/Presented At
Dangond, F., Hwang, D., Camelo, S., Pasinelli, P., Frosch, M. P., Stephanopoulos, G., Stephanopoulos, G., Brown, R. H., Jr, & Gullans, S. R. (2004). Molecular signature of late-stage human ALS revealed by expression profiling of postmortem spinal cord gray matter. Physiological genomics, 16(2), 229–239. https://doi.org/10.1152/physiolgenomics.00087.2001
Disciplines
Business Administration, Management, and Operations | Health and Medical Administration | Management Sciences and Quantitative Methods
PubMedID
14645737
Department(s)
Administration and Leadership
Document Type
Article