Apoptosis of oligodendrocytes and post-translational modifications of myelin basic protein in multiple sclerosis: possible role for the early stages of multiple sclerosis

Abstract

Recent studies outline apoptosis of oligodendrocytes (OLDs) as an early event prior to the formation of the demyelinated plaque and post-translational modifications (PTMs) of myelin basic protein as characteristic processes of normal-appearing white matter in multiple sclerosis (MS). We reviewed reports using the following keywords: apoptosis, PTMs, autoimmunity and multiple sclerosis in all possible combinations. Introductory basic scientific information is included for the non-experts. Given the standard and ongoing studies, we raise the hypothesis that, at least in some cases, defective apoptosis of OLDs, early in the course of the disease, and post-translationally modified molecules lead to the activation of immune responses and eventually to autoimmunity. Autoimmune reactions and epitope spreading that take place in the course of the disease might obscure the initial events and leave most investigators blind to etiopathogenesis. Our paper outlines the need for studies at the very early stages of the disease, as well as sequential ones, in order to give us a valuable hint about the clarification of the cause(s) of the different clinical subtypes of MS.