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Investigation of the role of apoptosis, necroptosis and DNA damage signaling pathways in multiple sclerosis

Author(s): Romina Dastmalchi, Arezou Sayad, Mir Davood Omrani, Soudeh Ghafouri-Fard, Shahram Arsang-Jang, Mehrdokht Mazdeh, Mohammad Taheri*

Multiple sclerosis (MS) as the most common autoimmune disorder in the central nervous system is a major health problem. MS is a complex disease with multiple environmental and genetic factors participating in it. In the present study, we evaluated the expression of 3 genes named BCL2, CASP2 and CASP8 in peripheral blood of 50 MS patients and 50 healthy controls to investigate the role of apoptosis, necroptosis and DNA damage signaling pathways in MS. Statistical analysis showed a significant increase in BCL2 and CASP2 expressions while a significant decrease in CASP8 expression in patients compared with the control group. The over-expression of the pro-apoptotic BCL2 is anticipated to induce accumulation of auto-reactive T cells which are involved in MS pathogenesis. Since caspase 8 is vital for the suppression of necroptotic pathway, defective activation of caspase 8 can cause inflammation and may be involved in the pathogenesis of MS disease. In brief, we have demonstrated altered levels of BCL2, CASP2 and CASP8 in MS patients compared with healthy subjects which potentiates these genes as biomarkers or therapeutic targets in MS. Further researchers are needed to evaluate the clinical relevance of these markers.