Nfe2L2 Protein is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
| NFE2L2 Protein (Nrf2) |
|---|
| Protein Name | Nuclear Factor Erythroid 2-Related Factor 2 |
| Gene | NFE2L2 |
| UniProt ID | Q16236 |
| PDB IDs | 4UDT, 5F75, 5H11 |
| Molecular Weight | 66 kDa |
| Subcellular Localization | Cytoplasm (inactive), nucleus (active) |
| Protein Family | bZIP transcription factor family |
NFE2L2 PROTEIN is a gene/protein encoding a key neuronal protein involved in synaptic function, signal transduction, and cellular homeostasis. Dysfunction of NFE2L2 PROTEIN is associated with neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, and related disorders.
Nrf2 is a bZIP transcription factor:
- Neh (Nrf2-ECH) domains: 6 regulatory domains
- bZIP domain: DNA binding and dimerization
- Transactivation domain: Activates transcription
- KEAP1 binding sites: Sensor for oxidative stress
- Antioxidant response: Master regulator of antioxidant genes
- Phase II detoxification: Induces detoxifying enzymes
- Proteostasis: Activates proteasome and autophagy
- Mitochondrial biogenesis: Regulates PGC-1α
- Inflammation suppression: Inhibits NF-κB
- Neuroprotective in AD models
- Impaired Nrf2 signaling in AD
- Therapeutic potential of activators
- Protects dopaminergic neurons
- Nrf2 activators in trials
- Dysregulated in ALS
- Therapeutic target
| Approach |
Status |
Description |
| Nrf2 activators (CDDO, sulforaphane) |
Clinical trials |
Activating Nrf2 pathway |
| KEAP1 inhibitors |
Research |
Releasing Nrf2 inhibition |
- 10488963: Nrf2 as master regulator. Nat Rev Drug Discov, 2009.
- 25622800: Nrf2 in neurodegeneration. Nat Rev Neurol, 2015.
The study of Nfe2L2 Protein has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.
- Li E et al.. "CRISPRi-based screens in iAssembloids to elucidate neuron-glia interactions." Neuron (2025). DOI: 10.1016/j.neuron.2024.12.016 PubMed: 39814010
- Deng PX et al.. "Artemisinin inhibits neuronal ferroptosis in Alzheimer's disease models by targeting KEAP1." Acta pharmacologica Sinica (2025). DOI: 10.1038/s41401-024-01378-6 PubMed: 39251858
- Cheng M et al.. "Quercetin Attenuates Oxidative Stress and Apoptosis in Brain Tissue of APP/PS1 Double Transgenic AD Mice by Regulating Keap1/Nrf2/HO-1 Pathway to Improve Cognitive Impairment." Behavioural neurology (2024). DOI: 10.1155/2024/5698119 PubMed: 39233848
- Gao Y et al.. "Targeting the bile acid receptor TGR5 with Gentiopicroside to activate Nrf2 antioxidant signaling and mitigate Parkinson's disease in an MPTP mouse model." Journal of advanced research (2026). DOI: 10.1016/j.jare.2025.05.039 PubMed: 40414345
- Jia H et al.. "Repurposing of epalrestat for neuroprotection in parkinson's disease via activation of the KEAP1/Nrf2 pathway." Journal of neuroinflammation (2025). DOI: 10.1186/s12974-025-03455-x PubMed: 40301912
- Zhu M et al.. "The NFE2L2 rs35652124 polymorphism and the risk of Parkinson's disease: a systematic review and meta-analysis." Neuroreport (2016). DOI: 10.1097/WNR.0000000000000627 PubMed: 27306592
- Ding T et al.. "Schisandrin B ameliorates Alzheimer's disease by suppressing neuronal ferroptosis and ensuing microglia M1 polarization." Phytomedicine (2025). DOI: 10.1016/j.phymed.2025.156780 PubMed: 40382817
- Uruno A, Yamamoto M. "The KEAP1-NRF2 System and Neurodegenerative Diseases." Antioxidants & redox signaling (2023). DOI: 10.1089/ars.2023.0234 PubMed: 36930785