Multiple Sclerosis and Neuroinflammation: The Overview of Current and Prospective Therapies

Abstract

Persistent neuroinflammation is now recognized as a chief pathological component of practically all neurodegenerative diseases. Neuroinflammation in the central nervous system (CNS), is accompanied with immune responses of glial cells. Glial cells respond to pathological stimuli through antigen presentation, and cytokine and chemokine signaling. Therefore, limiting CNS inflammation represents prospective therapeutic approach in diseases like Alzheimer's, amyotrophic lateral sclerosis, Parkinson's, ischemia, various psychiatric disorders and Multiple sclerosis (MS). As a complex disease, MS is characterized by neuroinflamation, demyelination and sequential axonal loss. Due to unknown etiology and the heterogeneous presentation of the disease, MS is hard to treat and the search for potential therapeutics is wide and meticulous. However, finding a proper antineuroinflammatory drug may bring an advance in selecting novel treatment regimens of ample of neurodegenerative diseases and neurological disorders. The present review gives the overview of the existing and potential therapies in MS, aimed to modulate neuroinflammation and ensure neuroprotection.

Animal models of multiple sclerosis: Focus on experimental autoimmune encephalomyelitis

“…In general, astrocytes are cells of the innate immune system that preserve homeostasis within the CNS. They are considered nontraditional antigen‐presenting cells; however, astrocytes are capable of modulating T cell and microglial immune response within the CNS (Bjelobaba et al, ; Chastain, Duncan, Rodgers, & Miller, ). Astrocytes serve to maintain the BBB in normal conditions, but in response to inflammation they produce cytokines, which allow T cell migration through the damaged BBB.…”

“…Considering the relevance of infectious factors contributing to MS, viruses have been thought to play a role in the initiation and progression of this disease (Bjelobaba, Savic, & Lavrnja, 2017). Consequently, suitable animal models that involve virus-induced demyelination are generated by Theiler's virus, canine distemper virus, and mouse hepatitis virus (Lassmann & Bradl, 2017).…”

Down-regulation of NTPDase2 and ADP-sensitive P2 Purinoceptors Correlate with Severity of Symptoms during Experimental Autoimmune Encephalomyelitis

“…Multiple sclerosis (MS) is a chronic autoimmune disease characterized by isolated plaques of demyelination and axonal loss in the brain and spinal cord (Lassmann et al, 2007 ; Lassmann, 2014 ). Although the exact cause of MS is still undetermined, the disease is mediated by adaptive immunity through the infiltration of T cells into the central nervous system (CNS; for review see, Bjelobaba et al, 2017 ). Clinical studies in MS and studies on a widely accepted animal model of MS, experimental autoimmune encephalomyelitis (EAE), demonstrate that the autoimmune process is primarily mediated by self-reactive Th1 and Th17 CD4 + cells which enter the CNS, where they become reactivated by resident antigen-presenting microglia, recurrently inducing microglial activation and consequent demyelination and axonal loss (McFarland and Martin, 2007 ).…”

Repurposing Fumaric Acid Esters to Treat Conditions of Oxidative Stress and Inflammation: A Promising Emerging Approach with Broad Potential

“…However, neuroinflammation and/or toxicity remain major concerns in this disease. The critical relevance of neuroinflammation to the etiology of MS, a disease for which DMF/MMF therapy is already approved, is undeniable [48]. Further, patients with MS are at considerably higher risk for neurotoxicity than are patients without the demyelinating disease [49].…”