Gene-microarray analysis of multiple sclerosis lesions yields new targets validated in autoimmune encephalomyelitis

@article{Lock2002GenemicroarrayAO,
  title={Gene-microarray analysis of multiple sclerosis lesions yields new targets validated in autoimmune encephalomyelitis},
  author={Christopher B. Lock and Guy Hermans and Rosetta Pedotti and Andrea Brendolan and Eric Schadt and Hideki Garren and Annette M Langer-Gould and Samuel Strober and Barbara Cannella and John D. Allard and Paul Klonowski and Angela Austin and Nagin Lad and Naftali Kaminski and Stephen J. Galli and Jorge R. Oksenberg and Cedric S Raine and Renu A. Heller and Lawrence Steinman},
  journal={Nature Medicine},
  year={2002},
  volume={8},
  pages={500-508}
}
Microarray analysis of multiple sclerosis (MS) lesions obtained at autopsy revealed increased transcripts of genes encoding inflammatory cytokines, particularly interleukin-6 and -17, interferon-γ and associated downstream pathways. Comparison of two poles of MS pathology—acute lesions with inflammation versus 'silent' lesions without inflammation—revealed differentially transcribed genes. Some products of these genes were chosen as targets for therapy of experimental autoimmune… 
Microarrays: Validation on target
  • M. Brazil
  • Medicine
    Nature Reviews Drug Discovery
  • 2002
TLDR
Gene-microarray analysis of multiple sclerosis lesions yields new targets validated in autoimmune encephalitis, suggesting that chips constructed by this chemical approach could find broad application in glycobiology, from research to drug discovery and diagnostics.
Altered Expression of Oligodendrocyte and Neuronal Marker Genes Predicts the Clinical Onset of Autoimmune Encephalomyelitis and Indicates the Effectiveness of Multiple Sclerosis–Directed Therapeutics
TLDR
Results show that neurons and oligodendrocytes are highly sensitive to CNS-directed autoimmunity before the development of clinical symptoms and immunopathology and reveal a role for soluble TNF in mediating the earliest changes in gene expression.
Exploiting genotypic differences to identify genes important for EAE development
TLDR
It is shown that a majority of the genes regulated in EAE are also regulated in diseased regions of human MS tissues, and the genes in the pool of 94 are more likely to be found regulated in MS patients than the genesregulated in only one or two of the mouse strains suggesting that analyzing gene expression under these multiple genetic conditions may lead to better identification of the gene critical for disease development.
Blood transcriptional signatures of multiple sclerosis: Unique gene expression of disease activity
TLDR
It is indicated that gene expression patterns in PBMCs contain information about a remote‐target disease process that may be useful for diagnosis and future tailoring of therapeutic strategies for MS.
Animal models of multiple sclerosis—Potentials and limitations
TLDR
Investigations in EAE are more suitable for the analysis of immunogenetic elements and for the study of histopathological features of the disease than for screening of new treatments, and deeper insight is provided into the pathogenic cellular and molecular mechanisms of EAE and potentially of MS.
Gene microarray analysis of multiple sclerosis lesions.
TLDR
The involvement of immune-related genes has been confirmed, and many new genes not previously associated with MS lesions have been identified, and microarray studies are significant in identifying potential new targets for therapy.
Quantitative and qualitative changes in gene expression patterns characterize the activity of plaques in multiple sclerosis.
Multiple sclerosis (MS) is a complex autoimmune disorder of the CNS with both genetic and environmental contributing factors. Clinical symptoms are broadly characterized by initial onset, and
Transcriptomic Meta-Analysis of Multiple Sclerosis and Its Experimental Models
TLDR
A meta-analysis based on a simple comparison of DEGs is over-conservative and the more experimental GSEA approach identified both, a priori anticipated as well as promising new candidate pathways.
Proteomic analysis of active multiple sclerosis lesions reveals therapeutic targets
TLDR
In vivo administration of hirudin or recombinant activated protein C reduced disease severity in experimental autoimmune encephalomyelitis and suppressed Th1 and Th17 cytokines in astrocytes and immune cells.
Gene-expression profiling of the early stages of MOG-induced EAE proves EAE-resistance as an active process
TLDR
Resistance to EAE (and possibly to MS) is an active process mediated by multiple genes up-regulated in peripheral lymphatic organs of resistant animals, and monitoring of the expression of these new candidate genes may serve as a tool for the disease progression and the pharmaceutical treatment.
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