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The Roles of Neutrophil-Derived Myeloperoxidase (MPO) in Diseases: The New Progress
Wei Lin1, Huili Chen2, Xijing Chen1
1Clinical Pharmacology Research Center, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing 210009, China.
Abstract:
Myeloperoxidase (MPO) is a heme-containing peroxidase, mainly expressed in neutrophils and, to a lesser extent, in monocytes. MPO is known to have a broad bactericidal ability via catalyzing the reaction of Cl- with H2O2 to produce a strong oxidant, hypochlorous acid (HOCl). However, the overproduction of MPO-derived oxidants has drawn attention to its detrimental role, especially in diseases characterized by acute or chronic inflammation. Broadly speaking, MPO and its derived oxidants are involved in the pathological processes of diseases mainly through the oxidation of biomolecules, which promotes inflammation and oxidative stress. Meanwhile, some researchers found that MPO deficiency or using MPO inhibitors could attenuate inflammation and tissue injuries. Taken together, MPO might be a promising target for both prognostic and therapeutic interventions. Therefore, understanding the role of MPO in the progress of various diseases is of great value. This review provides a comprehensive analysis of the diverse roles of MPO in the progression of several diseases, including cardiovascular diseases (CVDs), neurodegenerative diseases, cancers, renal diseases, and lung diseases (including COVID-19). This information serves as a valuable reference for subsequent mechanistic research and drug development.
Insights
Myeloperoxidase (MPO) drives disease by oxidizing biomolecules, promoting inflammation and oxidative stress. Inhibiting MPO may offer therapeutic benefits for various inflammatory and degenerative conditions.
Area of Science:
- Biochemistry
- Immunology
- Pathology
Background:
- Myeloperoxidase (MPO) is an enzyme primarily in neutrophils, crucial for bactericidal activity.
- MPO generates hypochlorous acid (HOCl), a potent oxidant, via hydrogen peroxide and chloride ions.
- Overproduction of MPO-derived oxidants contributes to inflammation and tissue damage in various diseases.
Purpose of the Study:
- To comprehensively review the multifaceted roles of MPO in disease progression.
- To highlight MPO's involvement in cardiovascular, neurodegenerative, cancer, renal, and lung diseases.
- To underscore MPO as a potential prognostic and therapeutic target.
Main Methods:
- Literature review and synthesis of existing research on MPO's function in disease.
- Analysis of MPO's impact on biomolecular oxidation, inflammation, and oxidative stress.
- Examination of studies involving MPO deficiency or inhibition in disease models.
Main Results:
- MPO-derived oxidants contribute to pathological processes by oxidizing biomolecules.
- Evidence suggests MPO deficiency or inhibition can reduce inflammation and tissue injury.
- MPO plays a significant role in the pathogenesis of diverse diseases, including CVDs, neurodegenerative disorders, cancers, and lung diseases.
Conclusions:
- MPO is implicated in the progression of numerous diseases through oxidative mechanisms.
- Targeting MPO presents a promising strategy for therapeutic intervention and disease management.
- Further research into MPO's mechanisms is valuable for drug development.
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