CSF Proteomics Identifies Specific and Shared Pathways for Multiple Sclerosis Clinical Subtypes.
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.
Dr. Orhan Öcalgiray Molecular Biology-Biotechnology and Genetics Research Center, Istanbul Technical University, Istanbul, Turkey.
Timucin
T
Avsar
Faculty of Engineering & Natural Sciences, Biological Sciences & Bioengineering, Sabancı University, Istanbul, Turkey.
İlknur Melis
İM
Durası
Department of Neurology, Cerrahpasa School of Medicine, Istanbul University, Istanbul, Turkey.
Uğur
U
Uygunoğlu
Department of Neurology, Cerrahpasa School of Medicine, Istanbul University, Istanbul, Turkey.
Melih
M
Tütüncü
Department of Neurology, Cerrahpasa School of Medicine, Istanbul University, Istanbul, Turkey.
Nuri Onat
NO
Demirci
Department of Neurology, Cerrahpasa School of Medicine, Istanbul University, Istanbul, Turkey.
Sabahattin
S
Saip
Medical Informatics Department, Acibadem University, Ataşehir, İstanbul, Turkey.
O Uğur
OU
Sezerman
Department of Neurology, Cerrahpasa School of Medicine, Istanbul University, Istanbul, Turkey.
Aksel
A
Siva
Dr. Orhan Öcalgiray Molecular Biology-Biotechnology and Genetics Research Center, Istanbul Technical University, Istanbul, Turkey; Molecular Biology and Genetics Department, Science and Letter Faculty, Istanbul Technical University, Istanbul, Turkey.
Eda
E
Tahir Turanlı
D000328:Adult; D019295:Computational Biology; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000145:classification / Q000378:metabolism*; D020528:Multiple Sclerosis, Chronic Progressive / Q000378:metabolism; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000378:metabolism; D040901:Proteomics; D058504:Th17 Cells / Q000378:metabolism