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Targeting GPX4-dependent ferroptosis by natural compounds in multiple sclerosis
Ning Zhou1, Yi-Rong Dong1, Jin-Rong Wang1
1State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Department of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China.
Abstract:
Multiple sclerosis (MS) is an autoimmune-mediated, heterogeneous, multifactorial central nervous system degenerative disease influenced by genetics and environment. Ferroptosis, an iron-dependent lipid peroxidation/reactive oxygen species-induced programmed cell death, exacerbates MS pathology. Glutathione peroxidase 4 (GPX4) regulates ferroptosis by clearing peroxides to sustain cells. Targeting GPX4-mediated ferroptosis, especially via safe, potent natural compounds, is a promising MS treatment. This review explores GPX4-dependent ferroptosis's role in MS progression and summarizes natural compounds for MS therapy.
Insights
This review discusses how ferroptosis, a cell death process regulated by Glutathione peroxidase 4 (GPX4), worsens multiple sclerosis (MS). It highlights natural compounds as potential therapies targeting GPX4 in MS treatment.
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.
