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Nrf2 as a therapeutic target for rheumatic diseases
María Luisa Ferrándiz1, Josep Nacher-Juan1, Maria José Alcaraz1
1Instituto Interuniversitario de Investigación de Reconocimiento Molecular y Desarrollo Tecnológico (IDM), Universitat Politècnica de València, Universitat de València, Av. Vicent A. Estellés s/n, 46100 Burjasot, Valencia, Spain.
Biochemical Pharmacology
|April 17, 2018
Summary
Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) regulates cellular protection. Activating Nrf2 shows therapeutic potential for rheumatic diseases by reducing inflammation and oxidative stress, despite challenges with current inducers.
Area of Science:
- Immunology
- Molecular Biology
- Rheumatology
Background:
- Rheumatic diseases cause chronic inflammation, pain, and tissue damage, impacting millions globally.
- Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is a key regulator of cellular defense mechanisms.
- Nrf2 plays a critical role in managing oxidative stress, inflammation, and immune responses relevant to rheumatic conditions.
Purpose of the Study:
- To explore the role of Nrf2 in the pathophysiology of rheumatic diseases.
- To evaluate the therapeutic potential of modulating the Nrf2 pathway in rheumatic conditions.
- To review current strategies and challenges in targeting Nrf2 for treating rheumatic diseases.
Main Methods:
- Literature review of studies investigating Nrf2 in experimental models of rheumatic diseases.
- Analysis of evidence on Nrf2's involvement in oxidative stress, inflammation, and immune regulation.
- Examination of Nrf2 activators and their effects, including potential off-target effects.
Main Results:
- Nrf2 deficiency exacerbates disease severity in experimental rheumatic conditions.
- Nrf2 activation demonstrates significant immunoregulatory and anti-inflammatory effects.
- Current Nrf2 inducers, often electrophilic, may cause undesirable off-target effects.
Conclusions:
- The Nrf2 pathway is a promising therapeutic target for rheumatic diseases.
- Pharmacologic regulation of Nrf2 offers potential benefits for managing inflammation and oxidative stress.
- Development of novel, targeted strategies for Nrf2 modulation is crucial to overcome limitations of existing inducers.
Keywords:
Nrf2OsteoarthritisOsteoporosisRheumatic conditionsRheumatoid arthritisSystemic lupus erythematosusMore Related Videos
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