Abstract
Multiple sclerosis (MS) is an immune-mediated, neuro-inflammatory, demyelinating and neurodegenerative disease of the central nervous system (CNS) with a heterogeneous clinical presentation and course. There is a remarkable phenotypic heterogeneity in MS, and the molecular mechanisms underlying it remain unknown. We aimed to investigate further the etiopathogenesis related molecular pathways in subclinical types of MS using proteomic and bioinformatics approaches in cerebrospinal fluids of patients with clinically isolated syndrome, relapsing remitting MS and progressive MS (n=179). Comparison of disease groups with controls revealed a total of 151 proteins that are differentially expressed in clinically different MS subtypes. KEGG analysis using PANOGA tool revealed the disease related pathways including aldosterone-regulated sodium reabsorption (p=8.02x10-5) which is important in the immune cell migration, renin-angiotensin (p=6.88x10-5) system that induces Th17 dependent immunity, notch signaling (p=1.83x10-10) pathway indicating the activated remyelination and vitamin digestion and absorption pathways (p=1.73x10-5). An emerging theme from our studies is that whilst all MS clinical forms share common biological pathways, there are also clinical subtypes specific and pathophysiology related pathways which may have further therapeutic implications.
Highlights
Multiple sclerosis (MS) is an immune-mediated neuro-inflammatory and neurodegenerative disease of the central nervous system (CNS) in which the major damage involves the myelin and axons [1, 2]
Our results revealed the presence of common disease pathways; renin angiotensin system and complement and coagulation cascade pathway shared by all disease subtypes
The samples comprised cerebrospinal fluid from 65 patients initially diagnosed with clinically isolated syndrome (CIS), 72 patients with relapsing remitting MS (RRMS), and 42 progressive MS (PMS) group which was compromised of 8 secondary progressive MS (SPMS) and 34 primary progressive (PPMS)
Summary
Multiple sclerosis (MS) is an immune-mediated neuro-inflammatory and neurodegenerative disease of the central nervous system (CNS) in which the major damage involves the myelin and axons [1, 2]. Decades of research have been conducted, only recently immunemediated and neurodegenerative processes of MS became more biologically and pathologically evident [3, 4]. It seems conceivable that in genetically susceptible individuals, release of CNS.
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