NRF2 Regulation Processes as a Source of Potential Drug Targets against Neurodegenerative Diseases
Abstract
:1. Neurodegenerative Diseases and Oxidative Stress as Common Pathological Pathway
2. The NRF2–ARE Pathway
3. Structure of NRF2
4. Neurodegenerative Diseases Hallmarks and Their Crosstalk with NRF2
4.1. Oxidative Stress
4.2. Neuroinflammation
4.2.1. NRF2 and Neuroinflammation: General Aspects
4.2.2. Nrf2 and Toll-Like Receptor Signaling
4.2.3. NRF2 and NFκB
4.3. Proteostasis
5. NRF2 Activation as a Useful Approach to Neurodegenerative Disease Therapy
5.1. KEAP1-Dependent Regulation
5.1.1. KEAP1 as an Oxidative Stress Sensor
5.1.2. KEAP1 Covalent Modifiers
Natural and Semisynthetic NRF2 Activators and Their Analogues
Synthetic NRF2 Activators
5.1.3. KEAP1 Protein–Protein Interaction Inhibitors
5.1.4. Epigenetic Control of KEAP 1 Expression
5.2. KEAP1-Independent Regulation
5.2.1. NRF2 Regulation by GSK-3β
5.2.2. KEAP1-Independent Regulation of NRF2 Stability
5.2.3. Miscellaneous ARE Transcription Regulators Connected to NRF2
5.2.4. Miscellaneous Pathways Regulating the Post-Translational Phosphorylation of NRF2
6. Conclusions
Funding
Conflicts of Interest
Abbreviations
References
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Compound | Disease | Clinical Trial | Ref |
---|---|---|---|
Pioglitazone | Type II diabetes | Approved | |
Several diseases | 300 clinical trials | -- | |
Tideglusib | AD | Phase II | NCT01350362 |
Congenital myotonic dystrophy | Phase II/III | NCT03692312 | |
Autism spectrum disorders | Phase II | NCT02586935 | |
Progressive supranuclear palsy | - | NCT01049399 | |
TDZD-8 | AD | Preclinical evaluation | |
SB216763 | AD | Preclinical evaluation | |
YQ138 | Brain ischemia | Preclinical evaluation | |
Obacunone | Natural product positioned toward several diseases | Preclinical evaluation |
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Cores, Á.; Piquero, M.; Villacampa, M.; León, R.; Menéndez, J.C. NRF2 Regulation Processes as a Source of Potential Drug Targets against Neurodegenerative Diseases. Biomolecules 2020, 10, 904. https://doi.org/10.3390/biom10060904
Cores Á, Piquero M, Villacampa M, León R, Menéndez JC. NRF2 Regulation Processes as a Source of Potential Drug Targets against Neurodegenerative Diseases. Biomolecules. 2020; 10(6):904. https://doi.org/10.3390/biom10060904
Chicago/Turabian StyleCores, Ángel, Marta Piquero, Mercedes Villacampa, Rafael León, and J. Carlos Menéndez. 2020. "NRF2 Regulation Processes as a Source of Potential Drug Targets against Neurodegenerative Diseases" Biomolecules 10, no. 6: 904. https://doi.org/10.3390/biom10060904
APA StyleCores, Á., Piquero, M., Villacampa, M., León, R., & Menéndez, J. C. (2020). NRF2 Regulation Processes as a Source of Potential Drug Targets against Neurodegenerative Diseases. Biomolecules, 10(6), 904. https://doi.org/10.3390/biom10060904