Abstract
CNS inflammation is a major driver of MS pathology. Differential immune responses, including the adaptive and the innate immune system, are observed at various stages of MS and drive disease development and progression. Next to these immune-mediated mechanisms, other mediators contribute to MS pathology. These include immune-independent cell death of oligodendrocytes and neurons as well as oxidative stress-induced tissue damage. In particular, the complex influence of oxidative stress on inflammation and vice versa makes therapeutic interference complex. All approved MS therapeutics work by modulating the autoimmune response. However, despite substantial developments in the treatment of the relapsing-remitting form of MS, approved therapies for the progressive forms of MS as well as for MS-associated concomitants are limited and much needed. Here, we summarize the contribution of inflammation and oxidative stress to MS pathology and discuss consequences for MS therapy development.
Highlights
Multiple sclerosis (MS) is a multifactorial autoimmune disease of the central nervous system (CNS) that is characterized by chronic inflammation, demyelination, and axon and neuronal loss
Systemic inflammation, proinflammatory cytokine release, and reactive oxygen species (ROS) signaling turn microglial physiological functions into toxic inflammatory insults [113]. These findings suggest that activated microglia and macrophages are orchestrating tissue injury through their oxidative burst during the development and progression of EAE and MS lesions
Even though MS is considered an immune-driven disease, several other mechanisms contribute to its pathology, including oxidative stress, immune-independent demyelination, and neuronal cell death
Summary
Multiple sclerosis (MS) is a multifactorial autoimmune disease of the central nervous system (CNS) that is characterized by chronic inflammation, demyelination, and axon and neuronal loss. 12 immunomodulatory agents are approved as disease-modifying therapies for MS Adjuvant drugs, such as antidepressants, are typically used to treat MS-associated CNP [4]. All of these therapeutics show either a limited efficiency or severe side effects. They do not target all MS symptoms, and treatment options for sensory impairments are limited and often not very effective [2, 4]. Oxidative Medicine and Cellular Longevity we will summarize the contribution of inflammation and oxidative stress to MS pathology and discuss current therapeutic developments that may improve MS therapy
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