ArticleJournal of neuroinflammation2022
Posttranslational modifications of proteins are key features in the identification of CSF biomarkers of multiple sclerosis.
Article in Journal of neuroinflammation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed, 14 citations in OpenAlex.
- Microbiota-Derived SCFAs in Multiple Sclerosis: From Immune Priming to Neurodegeneration.Molecular neurobiology · 2025Review
- Transthyretin, a novel prognostic marker of POCD revealed by time-series RNA-sequencing analysis.Molecular psychiatry · 2025Article
- New insights into the pharmacological inhibition of SRF activity: Key inhibitory targets and mechanisms.Vascular pharmacology · 2024Review
- Quantitative proteomics and multi-omics analysis identifies potential biomarkers and the underlying pathological molecular networks in Chinese patients with multiple sclerosis.BMC neurology · 2024Article
- Recent advances in serum response factor posttranslational modifications and their therapeutic potential in cardiovascular and neurological diseases.Vascular pharmacology · 2024Review
- Glycoproteomics in Cerebrospinal Fluid Reveals Brain-Specific Glycosylation Changes.International journal of molecular sciences · 2023Article
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Authors and funding
16 authors at 4 institutions in 1 country.
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Abstract
backgroundMultiple sclerosis is an inflammatory and degenerative disease of the central nervous system (CNS) characterized by demyelination and concomitant axonal loss. The lack of a single specific test, and the similarity to other inflammatory diseases of the central nervous system, makes it difficult to have a clear diagnosis of multiple sclerosis. Therefore, laboratory tests that allows a clear and definite diagnosis, as well as to predict the different clinical courses of the disease are of utmost importance. Herein, we compared the cerebrospinal fluid (CSF) proteome of patients with multiple sclerosis (in the relapse-remitting phase of the disease) and other diseases of the CNS (inflammatory and non-inflammatory) aiming at identifying reliable biomarkers of multiple sclerosis.
methodsCSF samples from the discovery group were resolved by 2D-gel electrophoresis followed by identification of the protein spots by mass spectrometry. The results were analyzed using univariate (Student's t test) and multivariate (Hierarchical Cluster Analysis, Principal Component Analysis, Linear Discriminant Analysis) statistical and numerical techniques, to identify a set of protein spots that were differentially expressed in CSF samples from patients with multiple sclerosis when compared with other two groups. Validation of the results was performed in samples from a different set of patients using quantitative (e.g., ELISA) and semi-quantitative (e.g., Western Blot) experimental approaches.
resultsAnalysis of the 2D-gels showed 13 protein spots that were differentially expressed in the three groups of patients: Alpha-1-antichymotrypsin, Prostaglandin-H2-isomerase, Retinol binding protein 4, Transthyretin (TTR), Apolipoprotein E, Gelsolin, Angiotensinogen, Agrin, Serum albumin, Myosin-15, Apolipoprotein B-100 and EF-hand calcium-binding domain-containing protein. ELISA experiments allowed validating part of the results obtained in the proteomics analysis and showed that some of the alterations in the CSF proteome are also mirrored in serum samples from multiple sclerosis patients. CSF of multiple sclerosis patients was characterized by TTR oligomerization, thus highlighting the importance of analyzing posttranslational modifications of the proteome in the identification of novel biomarkers of the disease.
conclusionsThe model built based on the results obtained upon analysis of the 2D-gels and in the validation phase attained an accuracy of about 80% in distinguishing multiple sclerosis patients and the other two groups.
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