ArticlePloS one2018
Orthologous proteins of experimental de- and remyelination are differentially regulated in the CSF proteome of multiple sclerosis subtypes.
Article in PloS one, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.
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Who cites it
19 citing papers in PubMed, 1 synthesis or guideline pooled it, 42 citations in OpenAlex.
- A Systematic Review of Tissue and Single Cell Transcriptome/Proteome Studies of the Brain in Multiple Sclerosis.Frontiers in immunology · 2022Pooled it
- Serum Proteomics Reveals Diagnostic Biomarkers and Molecular Pathways in Cerebral Palsy.Nature communications · 2025Article
- Single-Cell Multi-Omics Map of Cell Type-Specific Mechanistic Drivers of Multiple Sclerosis Lesions.Neurology(R) neuroimmunology & neuroinflammation · 2024Article
- Astrocytic TIMP-1 regulates production of Anastellin, an inhibitor of oligodendrocyte differentiation and FTY720 responses.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Expression of Bruton´s tyrosine kinase in different type of brain lesions of multiple sclerosis patients and during experimental demyelination.Frontiers in immunology · 2023Article
- Deciphering the Genetic Crosstalk between Microglia and Oligodendrocyte Precursor Cells during Demyelination and Remyelination Using Transcriptomic Data.International journal of molecular sciences · 2022Article
- Article
- Proteomics in Multiple Sclerosis: The Perspective of the Clinician.International journal of molecular sciences · 2022Review
- Cerebrospinal Fluid in Classical Trigeminal Neuralgia: An Exploratory Study on Candidate Biomarkers.Biomedicines · 2022Article
- Review
- A comprehensive review on the role of chemokines in the pathogenesis of multiple sclerosis.Metabolic brain disease · 2021Review
- CSF proteome in multiple sclerosis subtypes related to brain lesion transcriptomes.Scientific reports · 2021Article
- Digital Twins for Multiple Sclerosis.Frontiers in immunology · 2021Review
- Altered Expression of Ion Channels in White Matter Lesions of Progressive Multiple Sclerosis: What Do We Know About Their Function?Frontiers in cellular neuroscience · 2021Review
- Anti-Axl antibody treatment reduces the severity of experimental autoimmune encephalomyelitis.Journal of neuroinflammation · 2020Article
- Article
- Article
- Absence of miRNA-146a Differentially Alters Microglia Function and Proteome.Frontiers in immunology · 2020Article
- Cerebrospinal Fluid (CSF) Exchange with Artificial CSF Enriched with Mesenchymal Stem Cell Secretions Ameliorates Experimental Autoimmune Encephalomyelitis.International journal of molecular sciences · 2019Article
Corrections and comments
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Authors and funding
20 authors at 8 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveHere, we applied a multi-omics approach (i) to examine molecular pathways related to de- and remyelination in multiple sclerosis (MS) lesions; and (ii) to translate these findings to the CSF proteome in order to identify molecules that are differentially expressed among MS subtypes.
methodsTo relate differentially expressed genes in MS lesions to de- and remyelination, we compared transcriptome of MS lesions to transcriptome of cuprizone (CPZ)-induced de- and remyelination. Protein products of the overlapping orthologous genes were measured within the CSF by quantitative proteomics, parallel reaction monitoring (PRM). Differentially regulated proteins were correlated with molecular markers of inflammation by using MesoScale multiplex immunoassay. Expression kinetics of differentially regulated orthologous genes and proteins were examined in the CPZ model.
resultsIn the demyelinated and remyelinated corpus callosum, we detected 1239 differentially expressed genes; 91 orthologues were also differentially expressed in MS lesions. Pathway analysis of these orthologues suggested that the TYROBP (DAP12)-TREM2 pathway, TNF-receptor 1, CYBA and the proteasome subunit PSMB9 were related to de- and remyelination. We designed 129 peptides representing 51 orthologous proteins, measured them by PRM in 97 individual CSF, and compared their levels between relapsing (n = 40) and progressive MS (n = 57). Four proteins were differentially regulated among relapsing and progressive MS: tyrosine protein kinase receptor UFO (UFO), TIMP-1, apolipoprotein C-II (APOC2), and beta-2-microglobulin (B2M). The orthologous genes/proteins in the mouse brain peaked during acute remyelination. UFO, TIMP-1 and B2M levels correlated inversely with inflammation in the CSF (IL-6, MCP-1/CCL2, TARC/CCL17). APOC2 showed positive correlation with IL-2, IL-16 and eotaxin-3/CCL26.
conclusionsPathology-based multi-omics identified four CSF markers that were differentially expressed in MS subtypes. Upregulated TIMP-1, UFO and B2M orthologues in relapsing MS were associated with reduced inflammation and reflected reparatory processes, in contrast to the upregulated orthologue APOC2 in progressive MS that reflected changes in lipid metabolism associated with increased inflammation.
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