Proteomic strategies in multiple sclerosis and its animal models

Abstract

The early and precise diagnosis, the prognosis, and the clinical management of multiple sclerosis, remain a considerable challenge. In recent years, the development of novel and powerful proteomic techniques prompted the use of these approaches for the search of unique biomarkers in the cerebrospinal fluid of multiple sclerosis patients. A few studies have also utilized proteomics to delineate the profile of differentially expressed proteins in animal models of the human disease in order to gain global insights into affected pathways. The identification of differentially expressed proteins may be an initial step in the discovery of novel targets and mechanisms that play critical roles in the pathology of multiple sclerosis. Based on these findings, future investigations may elucidate the events leading to demyelination, axonal damage, and neurodegeneration, providing better insights into mechanisms governing the onset and progression of the disease. Although these proteomic studies provide valuable information, they are also faced with a number of challenges. The present review discusses some of the strengths and limitations of proteomic investigations as applied to multiple sclerosis.

Suppression of the Peripheral Immune System Limits the Central Immune Response Following Cuprizone-Feeding: Relevance to Modelling Multiple Sclerosis

“…Therefore, a quantitative ‘top-down’ proteomic approach was carried out to resolve protein species from whole brains of the CPZ-fed(±PT) mice. To date, proteome analyses of MS have mainly assessed tissue from late-stage post mortem brain samples and cerebrospinal fluid [89,96] or EAE animals [88,93,100,105]; these analyses provide useful insight into the ‘final readout’ of the disease or its autoimmune aspects [131,132,133] but not necessarily insight into the processes involved in disease aetiology and progression, including the role of oligodendrocytosis [1,49].…”

Animal models of multiple sclerosis—Potentials and limitations

“…In any case, due to its obvious limitations transcriptomics should be employed only with a clear and specific question in mind and carefully in view of the regulatory settings and potential pitfalls of the technique (Casciano and Woodcock, 2006;Fathallah-Shaykh, 2005). The same is true for the proteome approach (reviewed in Elkabes and Li, 2007;Linker et al, 2009a). In EAE, it has served to generate differential protein Table 2 Susceptibility genes of MS.…”

Cerebrospinal Fluid and Blood Biomarkers of Neuroaxonal Damage in Multiple Sclerosis

“…Among the wide range of proteins that have been found to be exclusively present in the CSF of MS patients [125, 189, 191–194], only some of them are expressed on neurons (contactin-1, neurofascin, neurotrimin, and chromogranins/secretogranins) [193–195]. It was recently shown that contactin-2 was recognised by both autoantibodies and Th1/Th17 T-cells in MS patients [36, 37] and neurofascin-specific autoantibodies were identified in MS patients [196].…”

“…Recently, a rapid development of proteomic approaches refocused biomarker research interest to the use of novel methods in the discovery of potential MS-specific biomarkers in biological fluids and especially in the CSF [ 189 , 190 ]. Among the wide range of proteins that have been found to be exclusively present in the CSF of MS patients [ 125 , 189 , 191 – 194 ], only some of them are expressed on neurons (contactin-1, neurofascin, neurotrimin, and chromogranins/secretogranins) [ 193 – 195 ]. It was recently shown that contactin-2 was recognised by both autoantibodies and Th1/Th17 T-cells in MS patients [ 36 , 37 ] and neurofascin-specific autoantibodies were identified in MS patients [ 196 ].…”