The role of the complement system in Multiple Sclerosis: A review

Area of Science:

• Neuroimmunology
• Complement System Biology
• Neurodegenerative Diseases

Background:

• The complement system is implicated in neuroinflammation and neurodegeneration.
• Its role in progressive multiple sclerosis (MS) is not fully understood, with limited treatment options.
• Evidence links complement activation to MS lesions in the brain.

Purpose of the Study:

• To review the role of complement activation in multiple sclerosis (MS) pathogenesis, particularly progressive MS.
• To explore the dual "double-edge sword" effects of complement in MS.
• To discuss complement inhibitors as potential therapeutic strategies for MS.

Main Methods:

• Review of immunohistochemical analyses of post-mortem MS brains.
• Analysis of in vivo serum and cerebrospinal fluid biomarker studies.
• Evaluation of animal models of Experimental Autoimmune Encephalomyelitis (EAE) and complement knock-out studies.

Main Results:

• Complement system activation shows a "double-edge sword" effect in MS.
• It aids in debris clearance via phagocytosis but can also cause demyelination and synapse loss.
• Complement may interact with MS risk factors like Epstein Barr Virus (EBV) and activate B cells.

Conclusions:

• The complement system is significantly involved in MS pathogenesis.
• Targeting the complement system with inhibitors is a promising therapeutic avenue for MS.
• Further research is needed on complement effector roles and CNS drug delivery for MS treatment.