Mechanisms of Neurodegeneration in Multiple Sclerosis

Abstract

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system, which results in the formation of primary demyelinating lesions in the white and gray matter, as well as diffuse axonal and neuronal damage. Although there has been substantial progress in drug research in relapsing-remitting MS, treatment of progressive forms of the disease, can be challenging. Diffuse and compartmentalized lymphocyte and macrophage infiltration of the CNS tissue inhibits the differentiation of myelinating mature oligodendrocytes, disrupting the process of remyelination. Chronic inflammation that occurs behind a closed blood-brain barrier (BBB) leads to microglia activation, which increases mitochondrial damage to axons and neurons, and therefore triggers chronic oxidative stress and histotoxic hypoxia. Thus, raising awareness about the mechanisms of neurodegeneration appears relevant. In the late stages of MS, it is caused by chronic neuroaxonal damage, disruption of the regenerative ability of the CNS, and to a great extent determines the disease outcome.