844 Proteomics Clin. Appl. 2015, 9, 844–847 DOI 10.1002/prca.201400171 How can proteomics elucidate the complexity of multiple sclerosis? Alessandro S. Farias and Leonilda M. B. Santos Neuroimmunomodulation Group and Neuroimmunology Unit, Department of Genetics, Evolution and Bioagents, University of Campinas, Campinas, S ˜ ao Paulo, Brazil Received: October 30, 2014 Revised: April 28, 2015 Accepted: May 11, 2015 Multiple sclerosis affects more than 2.5 million people worldwide. Although multiple sclerosis was described almost 150 years ago, there are many knowledge gaps regarding its etiology, diagnosis, prognosis, and pathogenesis. Multiple sclerosis is an inflammatory, demyelinating, neurodegenerative disease of the CNS. During the last several decades, experimental mod- els of multiple sclerosis have contributed to our understanding of the inflammatory disease mechanisms and have aided drug testing and development. However, little is known about the neurodegenerative mechanisms that operate during the evolution of the disease. Currently, all therapeutic approaches are primarily based on the inflammatory aspect of the disease. During the last decade, proteomics has emerged as a promising tool for revealing molecular pathways as well as identifying and quantifying differentially expressed proteins. Therefore, proteomics may be used for the discovery of biomarkers, potential drug targets, and new regulatory mecha- nisms. To date, a considerable number of proteomics studies have been conducted on samples from experimental models and patients with multiple sclerosis. These data form a solid base for further careful analysis and validation. Keywords: Experimental autoimmune encephalomyelitis / Inflammation / Multiple sclerosis / Neurodegeneration / Proteomics Multiple sclerosis is a complex disease in many aspects. Jean- Martin Charcot described multiple sclerosis almost 150 years ago (1868); however, its etiology is still unknown, although it is unlikely that multiple sclerosis is associated with a unique causative event. Familial aggregation studies have demon- strated that the disease clusters in families. During the 1970s, an association was first found with the human leucocyte anti- gen DR2 isotype, and this association was refined in recent years using DNA-based typing methods to the DRB1*1501 [1–3]. Recently, large-scale collaborative genome-wide stud- ies have enabled the discovery of many nonhuman leucocyte antigen susceptibility variants associated with multiple scle- rosis [4]. These variants are mostly associated with immuno- logical processes and are frequently associated with other Correspondence: Dr. Alessandro S Farias, Departamento de Gen ´ etica, Evoluc ¸˜ ao e Bioagentes, Instituto de Biologia-UNICAMP, Campinas, SP, CEP 13083-970, Brazil E-mail: asfarias@unicamp.br Fax: +55-19-35216185 Abbreviations: CSF, cerebrospinal fluid; EAE, experimental au- toimmune encephalomyelitis autoimmune diseases [5–7]. However, the analysis of these data has revealed only a moderate effect on the multiple scle- rosis odds ratio at best [8, 9]. Nonetheless, the fact that the disease frequency varies worldwide and the high discordance rate observed among monozygotic twins indicates a potential environmental influence on multiple sclerosis development [10, 11]. During the last several decades, many environmental factors (e.g. sunlight exposure, diet, infections, and lifestyle) have been associated with multiple sclerosis risk to some ex- tent. However, none of these factors alone have shown a high odds ratio [2, 12]. Thus, genetic and epidemiological studies have indicated that the disease must be a result of a com- plex genetic predisposition combined with an environmental trigger [7, 13, 14]. Multiple sclerosis is considered to be a demyelinating au- toimmune disease. Similar to the majority of autoimmune pathologies, multiple sclerosis is more common in women. Most of the patients (85%) present with a relapse-remitting clinical manifestation of the disease, and immunomodulatory or immunosuppressive therapies are effective in partially con- trolling the clinical manifestations of the disease [14, 15]. In parallel, there is an important neurodegenerative aspect of the C  2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim www.clinical.proteomics-journal.com