CSF SERPINA3 levels are increased in patients with progressive multiple sclerosis

ABSTRACT: One of the most challenging aspects in multiple sclerosis (MS) research is to understand the mechanisms leading to neurodegeneration and subsequent tissue repair. Here, we aimed to identify biomarkers associated with the progressive phases of the disease that may have neuroprotective potential. To achieve this, we performed a bioinformatic approach integrating transcriptional and proteomic profiles obtained during the course of experimental autoimmune encephalomyelitis (EAE) combined with gene expression microarray data from neuronal differentiation. Integrative analysis of omics data identified two molecules, serine (or cysteine) peptidase inhibitor, clade A, member 3N (Serpina3n) and S100 calcium binding protein A4 (S100A4), as biomarkers up-regulated in chronic progressive EAE whose expression was also induced during neuronal differentiation. Immunofluorescence studies revealed a primarily neuronal expression of Serpina3n and S100A4 during EAE as reflected by their co-localization with β-III-Tubulin in neurons from cerebellum, hippocampus and spinal cord tissues during EAE. Finally, levels of SERPINA3, the human ortholog of murine Serpina3n also known as α1-antichymotrypsin, and S100A4 were increased in cerebrospinal fluid of MS patients compared with non-inflammatory neurological controls. However, only SERPINA3 showed differences across MS clinical forms and levels were significantly elevated in patients with progressive forms of the disease, particularly in patients with primary progressive MS, compared with relapsing-remitting MS and neurological controls. Altogether, these results point to a role of SERPINA3 as biomarker associated with the progressive forms of MS that may also have neuroregenerative potential

INSTRUMENT(S): Orbitrap Eclipse

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Brain, Generation Of Neurons

DISEASE(S): Multiple Sclerosis

SUBMITTER: Eva Borràs  

LAB HEAD: Eduard Sabido

PROVIDER: PXD018173 | Pride | 2021-02-01

REPOSITORIES: Pride