New Insights into Multiple Sclerosis Mechanisms: Lipids on the Track to Control Inflammation and Neurodegeneration

Abstract

Multiple sclerosis (MS) is a central nervous system disease with complex pathogenesis, including two main processes: immune-mediated inflammatory demyelination and progressive degeneration with axonal loss. Despite recent progress in our understanding and management of MS, availability of sensitive and specific biomarkers for these both processes, as well as neuroprotective therapeutic options targeted at progressive phase of disease, are still being sought. Given their abundance in the myelin sheath, lipids are believed to play a central role in underlying immunopathogenesis in MS and seem to be a promising subject of investigation in this field. On the basis of our previous research and a review of the literature, we discuss the current understanding of lipid-related mechanisms involved in active relapse, remission, and progression of MS. These insights highlight potential usefulness of lipid markers in prediction or monitoring the course of MS, particularly in its progressive stage, still insufficiently addressed. Furthermore, they raise hope for new, effective, and stage-specific treatment options, involving lipids as targets or carriers of therapeutic agents.

Cytokine Profile in Patients with Multiple Sclerosis Following Exercise: A Systematic Review of Randomized Clinical Trials

“…Another proinflammatory cytokine that plays an important role in the immunopathology is IL-17, which is found in the CSF and blood of PwMS patients, with a large increase during relapses [49]. Contrary to previous expectations [11], this study showed a decrease in IL-17 serum levels, which had a beneficial impact on the amount of inflammation in PwMS patients who were in the stable/remission phase and were relapse-free for at least 2 months.…”

Lipid signatures of chronic pain in female adolescents with and without obesity

“…Sphingolipids such as sphingomyelin and ceramides are a major component of the central nervous system, where they are abundant in the plasma membrane of myelin sheaths and serve as possible biomarkers for the demyelination that occurs in multiple sclerosis [ 31 , 32 ]. Several sphingolipid species elevated in patients with multiple sclerosis include, but are not limited to: Cer 16:0, Cer 18:1, Cer 24:0, SM 20:0, SM 22:0, SM 24:0, SM 24:1 [ 33 , 34 ]. We similarly observed increases in Ceramide species contianing 16:0, 18:1, 24:0, 20:0, and 22:0 acyl chains in chronic pain with or without obesity.…”

Phytocannabinoids and Cannabis-Based Products as Alternative Pharmacotherapy in Neurodegenerative Diseases: From Hypothesis to Clinical Practice

“…MS is a chronic autoimmune and progressive neurological disorder that affects more than 3 million people worldwide and is considered the most prevalent neurodegenerative disease in young adults ( Reich et al, 2018 ). Disturbances in the neurovascular unit allow the infiltration of auto-reactive T cells into the CNS, which is facilitated by the activity of endothelial adhesion molecules (ICAM-1 and VCAM-1) and matrix metalloproteinases (MMP-2 and MMP-9), therefore promoting the degradation of myelin sheath and multifocal demyelinating lesions, mostly in the white matter, due to several immune-mediated mechanisms already postulated, such as cytokine release, cytotoxic attack of CD8 + T cells and macrophage-induced digestion of surface myelin antigens ( Podbielska et al, 2021 ; Figure 1 ).…”