The Role of Pro-and Anti-Apoptotic Mediators in Patients with Multiple Sclerosis

Background: Multiple sclerosis (MS) is a chronic neurological disorder characterized by myelin destruction and a variable degree of oligodendrocyte death. Programmed cell death (apoptosis) is critical for the normal development and homeostasis of the immune system. Apoptosis of autoreactive T cells in the CNS is likely to be important in preventing the development of MS. The death receptor (Fas) and its ligand (Fas-L) interaction results in activation-induced apoptosis and their abnormal expression together with nuclear factor (NF-кB) and Bcl-2 may be involved in the pathogenesis and the clinical course of MS. Objective: This work aim at clarifying the role of pro- and anti-apoptotic mediators in pathogenesis of MS. Methods: We studied the level and expression of Fas, Fas-L, NF-кB and Bcl-2 using RT-PCR, morphological changes of apoptosis in peripheral blood mononuclear cells (PBMCs), DNA fragmentation in 24 patients with MS divided into 3 groups: in relapse, in remission and secondary progressive cases. In addition, a group of 16 healthy cases served as controls. Results: We found that Fas & Fas-L were significantly decreased in patients with multiple sclerosis compared with healthy control subjects. While NF-кB and Bcl-2 were significantly increased in patients compared with healthy control subjects. Also, DNA fragmentation showed significant decrease in patients versus control. Conclusion: Impaired apoptosis detected by Fas, Fas-L, NF-кB and Bcl-2 mediators and DNA fragmentation, play an important role in the pathogenesis of MS. (Egypt J Neurol Psychiat Neurosurg. 2010; 47(2): 261-266)