17
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Proteomics of Multiple Sclerosis: Inherent Issues in Defining the Pathoetiology and Identifying (Early) Biomarkers

      review-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Multiple Sclerosis (MS) is a demyelinating disease of the human central nervous system having an unconfirmed pathoetiology. Although animal models are used to mimic the pathology and clinical symptoms, no single model successfully replicates the full complexity of MS from its initial clinical identification through disease progression. Most importantly, a lack of preclinical biomarkers is hampering the earliest possible diagnosis and treatment. Notably, the development of rationally targeted therapeutics enabling pre-emptive treatment to halt the disease is also delayed without such biomarkers. Using literature mining and bioinformatic analyses, this review assessed the available proteomic studies of MS patients and animal models to discern (1) whether the models effectively mimic MS; and (2) whether reasonable biomarker candidates have been identified. The implication and necessity of assessing proteoforms and the critical importance of this to identifying rational biomarkers are discussed. Moreover, the challenges of using different proteomic analytical approaches and biological samples are also addressed.

          Related collections

          Most cited references296

          • Record: found
          • Abstract: found
          • Article: found
          Is Open Access

          STRING v11: protein–protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets

          Abstract Proteins and their functional interactions form the backbone of the cellular machinery. Their connectivity network needs to be considered for the full understanding of biological phenomena, but the available information on protein–protein associations is incomplete and exhibits varying levels of annotation granularity and reliability. The STRING database aims to collect, score and integrate all publicly available sources of protein–protein interaction information, and to complement these with computational predictions. Its goal is to achieve a comprehensive and objective global network, including direct (physical) as well as indirect (functional) interactions. The latest version of STRING (11.0) more than doubles the number of organisms it covers, to 5090. The most important new feature is an option to upload entire, genome-wide datasets as input, allowing users to visualize subsets as interaction networks and to perform gene-set enrichment analysis on the entire input. For the enrichment analysis, STRING implements well-known classification systems such as Gene Ontology and KEGG, but also offers additional, new classification systems based on high-throughput text-mining as well as on a hierarchical clustering of the association network itself. The STRING resource is available online at https://string-db.org/.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: found

            Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria

            The 2010 McDonald criteria for the diagnosis of multiple sclerosis are widely used in research and clinical practice. Scientific advances in the past 7 years suggest that they might no longer provide the most up-to-date guidance for clinicians and researchers. The International Panel on Diagnosis of Multiple Sclerosis reviewed the 2010 McDonald criteria and recommended revisions. The 2017 McDonald criteria continue to apply primarily to patients experiencing a typical clinically isolated syndrome, define what is needed to fulfil dissemination in time and space of lesions in the CNS, and stress the need for no better explanation for the presentation. The following changes were made: in patients with a typical clinically isolated syndrome and clinical or MRI demonstration of dissemination in space, the presence of CSF-specific oligoclonal bands allows a diagnosis of multiple sclerosis; symptomatic lesions can be used to demonstrate dissemination in space or time in patients with supratentorial, infratentorial, or spinal cord syndrome; and cortical lesions can be used to demonstrate dissemination in space. Research to further refine the criteria should focus on optic nerve involvement, validation in diverse populations, and incorporation of advanced imaging, neurophysiological, and body fluid markers.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              The blood-brain barrier.

              Blood vessels are critical to deliver oxygen and nutrients to all of the tissues and organs throughout the body. The blood vessels that vascularize the central nervous system (CNS) possess unique properties, termed the blood-brain barrier, which allow these vessels to tightly regulate the movement of ions, molecules, and cells between the blood and the brain. This precise control of CNS homeostasis allows for proper neuronal function and also protects the neural tissue from toxins and pathogens, and alterations of these barrier properties are an important component of pathology and progression of different neurological diseases. The physiological barrier is coordinated by a series of physical, transport, and metabolic properties possessed by the endothelial cells (ECs) that form the walls of the blood vessels, and these properties are regulated by interactions with different vascular, immune, and neural cells. Understanding how these different cell populations interact to regulate the barrier properties is essential for understanding how the brain functions during health and disease.
                Bookmark

                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                Int J Mol Sci
                Int J Mol Sci
                ijms
                International Journal of Molecular Sciences
                MDPI
                1422-0067
                09 July 2021
                July 2021
                : 22
                : 14
                : 7377
                Affiliations
                [1 ]School of Medicine, Western Sydney University, Locked Bag 1797, Penrith, NSW 2751, Australia; monokesh.sen@ 123456westernsydney.edu.au (M.K.S.); m.almuslehi@ 123456westernsydney.edu.au (M.S.M.A.); d.mahns@ 123456westernsydney.edu.au (D.A.M.)
                [2 ]Department of Physiology & Pharmacology, College of Veterinary Medicine, University of Diyala, Baqubah 32001, Diyala, Iraq
                [3 ]School of Science, Western Sydney University, Locked Bag 1797, Penrith, NSW 2751, Australia; p.shortland@ 123456westernsydney.edu.au
                [4 ]Departments of Health Sciences and Biological Sciences, Faculties of Applied Health Sciences and Mathematics & Science, Brock University, St. Catharines, ON L2S 3A1, Canada
                Author notes
                [* ]Correspondence: jcoorssen@ 123456brocku.ca
                [†]

                Current address: Charles Perkins Centre, School of Medical Sciences, University of Sydney, Sydney, NSW 2006, Australia.

                Author information
                https://orcid.org/0000-0003-3988-9196
                https://orcid.org/0000-0002-7598-9744
                https://orcid.org/0000-0003-2131-9638
                https://orcid.org/0000-0001-8048-7370
                Article
                ijms-22-07377
                10.3390/ijms22147377
                8306353
                34298997
                64d41f3e-5d7e-4af5-98f2-efd1b9a306ff
                © 2021 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( https://creativecommons.org/licenses/by/4.0/).

                History
                : 24 April 2021
                : 29 June 2021
                Categories
                Review

                Molecular biology
                proteoforms,bioinformatics,cuprizone,experimental autoimmune encephalomyelitis,top-down proteomics,protein species,post-translational modifications,bottom-up proteomics,neurodegenerative disease

                Comments

                Comment on this article