Ten years of proteomics in multiple sclerosis

Abstract

Multiple sclerosis, which is the most common cause of chronic neurological disability in young adults, is an inflammatory, demyelinating, and neurodegenerative disease of the CNS, which leads to the formation of multiple foci of demyelinated lesions in the white matter. The diagnosis is based currently on magnetic resonance image and evidence of dissemination in time and space. However, this could be facilitated if biomarkers were available to rule out other disorders with similar symptoms as well as to avoid cerebrospinal fluid analysis, which requires an invasive collection. Additionally, the molecular mechanisms of the disease are not completely elucidated, especially those related to the neurodegenerative aspects of the disease. The identification of biomarker candidates and molecular mechanisms of multiple sclerosis may be approached by proteomics. In the last 10 years, proteomic techniques have been applied in different biological samples (CNS tissue, cerebrospinal fluid, and blood) from multiple sclerosis patients and in its experimental model. In this review, we summarize these data, presenting their value to the current knowledge of the disease mechanisms, as well as their importance in identifying biomarkers or treatment targets.

Anoctamin 2 identified as an autoimmune target in multiple sclerosis

“…S14A), reinforcing its potential role in MS etiopathogenesis. One of the main focus areas in MS research is the identification of molecular biomarker candidates, which would facilitate diagnosis and prognostic assessments in MS (9). CNS tissue, and in particular the MS lesion tissue forming the actual sites of disease, is an outstanding source to search for specific markers of disease-related mechanisms and pathophysiology in MS (10, 11).…”

Integrative Analysis of Multi-omics Data for Discovery and Functional Studies of Complex Human Diseases

“…Pan, Brentnall, & Chen, 2015; Petricoin et al, 2002; Tsai et al, 2015), multiple sclerosis (Farias, Pradella, Schmitt, Santos, & Martins-de-Souza, 2014) and schizophrenia (Al Awam et al, 2015; Nascimento & Martins-de-Souza, 2015). In an early study of ovarian cancer, an independently trained proteomic profile of serum samples was able to prospectively classify ovarian cancer cases and controls (Petricoin et al, 2002).…”

“…On the contrary, proteomic studies of multiple sclerosis and schizophrenia have not established any reliable protein biomarkers to classify patients after years of investigation of different biological samples (e.g. CNS tissue, cerebrospinal fluid, peripheral blood, plasma and serum) (Farias et al, 2014; Nascimento & Martins-de-Souza, 2015). However, these studies have found many protein candidates, which can potentially improve prognosis, diagnosis, and effectiveness of treatment.…”

Body fluid biomarkers in multiple sclerosis: how far we have come and how they could affect the clinic now and in the future

“…However, even once a new biomarker candidate has been discovered, it is often not sufficiently validated, partially because of the lack of good strategies to prioritize which candidate will be worth the effort, time and money spent on such “high risk” markers. In recent years, numerous studies have exploited “omics” techniques, including genomics, trancriptomics, lipidomics and proteomics leading to a large number of potential new biomarker candidates [271-274]. Thus, the issue of how to prioritize and validate potential biomarkers has become an even greater priority for the field.…”

“…Maybe not surprising, biomarker discovery has primarily focused on clinical studies, and studies using animal models such as EAE are underrepresented, most likely because of a perception that molecules discovered in preclinical models may not apply to human MS [271,275]. However, models such as EAE, have been extensively used to unravel disease mechanisms underlying the human disease and to develop drugs, particularly for MS [276].…”