Targeting GPX4-dependent ferroptosis by natural compounds in multiple sclerosis

Area of Science:

• Neuroimmunology
• Cellular Biology
• Pharmacology

Background:

• Multiple sclerosis (MS) is a complex central nervous system disease involving autoimmune processes, genetics, and environmental factors.
• Ferroptosis, a form of programmed cell death driven by iron and lipid peroxidation, significantly contributes to MS pathology.
• Glutathione peroxidase 4 (GPX4) is a key regulator of ferroptosis, protecting cells by neutralizing reactive oxygen species.

Purpose of the Study:

• To elucidate the role of GPX4-dependent ferroptosis in the progression of multiple sclerosis.
• To review and identify natural compounds with therapeutic potential for MS by targeting ferroptosis.
• To explore novel therapeutic strategies for MS based on modulating ferroptosis pathways.

Main Methods:

• Literature review of studies on MS, ferroptosis, GPX4, and natural compounds.
• Analysis of the mechanisms linking ferroptosis to MS pathogenesis.
• Synthesis of information on natural product efficacy and safety in preclinical MS models.

Main Results:

• Ferroptosis exacerbates neurodegeneration and inflammation in MS.
• GPX4 inhibition promotes ferroptosis, worsening MS.
• Several natural compounds show promise in mitigating ferroptosis and MS symptoms.

Conclusions:

• Targeting GPX4-mediated ferroptosis presents a viable therapeutic avenue for MS.
• Natural compounds offer a promising strategy for developing safe and effective MS treatments.
• Further research into natural product-based ferroptosis inhibitors is warranted for MS therapy.