Cerebrospinal fluid biomarkers of disease activity and progression in amyotrophic lateral sclerosis

Journal article

Funding Information: This work was supported by FCT - Fundação para a Ciência e a Tecnologia, I.P., through iNOVA4Health (UIDB/04462/2020, UIDP/04462/2020) and LS4FUTURE Associated Laboratory (LA/P/0087/2020). Funding Information: The development of resources of the Glyco@Expasy initiative that includes GlyConnect and GlyConnect Compozitor, is supported by the Swiss Federal Government through the State Secretariat for Education, Research and Innovation (SERI ). Expasy is maintained by the Swiss Institute of Bioinformatics and hosted at the Vital-IT Competency Center. Funding Information: We thank: Prof. Nicolle H. Packer and Dr. Katherine Wongtrakul-Kish, School of Natural Sciences, Faculty of Science, & Engineering, Macquarie University, Sydney 2109, Australia, for their suggestions and critical reading of the manuscript; Dr. Julien Mariethoz for his contribution to integrating the brain dataset in GlyConnect. This work was supported by FCT - Fundação para a Ciência e a Tecnologia, I.P. through iNOVA4Health (UIDB/04462/2020, UIDP/04462/2020) and LS4FUTURE Associated Laboratory (LA/P/0087/2020). The development of resources of the Glyco@Expasy initiative that includes GlyConnect and GlyConnect Compozitor, is supported by the Swiss Federal Government through the State Secretariat for Education, Research and Innovation (SERI). Expasy is maintained by the Swiss Institute of Bioinformatics and hosted at the Vital-IT Competency Center. Publisher Copyright: © 2023 The AuthorsGlycosylation is a common post-translational modification of brain proteins including cell surface adhesion molecules, synaptic proteins, receptors and channels, as well as intracellular proteins, with implications in brain development and functions. Using advanced state-of-the-art glycomics and glycoproteomics technologies in conjunction with glycoinformatics resources, characteristic glycosylation profiles in brain tissues are increasingly reported in the literature and growing evidence shows deregulation of glycosylation in central nervous system disorders, including aging associated neurodegenerative diseases. Glycan signatures characteristic of brain tissue are also frequently described in cerebrospinal fluid due to its enrichment in brain-derived molecules. A detailed structural analysis of brain and cerebrospinal fluid glycans collected in publications in healthy and neurodegenerative conditions was undertaken and data was compiled to create a browsable dedicated set in the GlyConnect database of glycoproteins (https://glyconnect.expasy.org/brain). The shared molecular composition of cerebrospinal fluid with brain enhances the likelihood of novel glycobiomarker discovery for neurodegeneration, which may aid in unveiling disease mechanisms, therefore, providing with novel therapeutic targets as well as diagnostic and progression monitoring tools.publishersversionpublishe

Authors: Dreger, M; Steinbach, R; Otto, M; Turner, MR; Grosskreutz, J

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: BMJ Publishing Group
• Journal: Journal of Neurology, Neurosurgery and Psychiatry
• Volume: 93
• Issue: 4
• Pages: 422-435
• Publication date: 2022-02-01
• DOI: 10.1136/jnnp-2021-327503
• EISSN: 1468-330X
• ISSN: 0022-3050
• Language: English
• Keywords: Biomarker discovery; Biomarker; Amyotrophic lateral sclerosis; Clinical endpoint; Biology; Internal medicine; Pathology; Bioinformatics; Medicine; Surrogate endpoint; Clinical study design; Clinical trial; Proteomics; Oncology; Precision medicine; Disease