Nrf2 (nuclear factor erythroid 2-related factor 2) is a transcription factor that regulates the expression of antioxidant proteins and detoxifying enzymes. Under normal conditions, Nrf2 is retained in the cytoplasm by its inhibitor, Keap1 (Kelch-like ECH-associated protein 1). Under oxidative stress, Nrf2 is released, translocates to the nucleus, and activates the expression of genes that protect against oxidative damage. The aging process is closely linked to increased oxidative stress and inflammation. Studies indicate that reduced Nrf2 activity correlates with aging, suggesting that enhancing Nrf2 function may mitigate age-related cellular damage.
Fig. 1 Nrf2 activation as an approach to anti-aging therapy. (Zinovkin RA, et al., 2022)
CD BioSciences is devoted to offering anti-aging drug discovery services. We help clients develop innovative therapeutics targeting Nrf2 pathways to promote healthy aging and mitigate age-related diseases.
Types of Anti-Aging Drugs Targeting Nrf2 That We Can Develop
- We help clients develop Nrf2 activators to enhance the expression of antioxidant genes and mitigate oxidative stress. The Nrf2 activators can reduce oxidative stress and inflammation levels, which have the potential to be anti-aging agents.
- Nrf2 activity is regulated by its interaction with the Keap1 protein, which targets Nrf2 for ubiquitination and degradation. We also help clients develop drugs to disrupt the Keap1-Nrf2 interaction, increasing its nuclear concentration and transcriptional activity.
How Do We Screen Anti-Aging Drugs Targeting Nrf2?
High-throughput screening
Utilizing high-throughput screening, we can rapidly evaluate thousands of potential drug candidates for their ability to modulate Nrf2 activity. Our approach allows clients to identify leads that can be further developed into anti-aging therapeutics.
Cell-based drug screening
We employ cell-based assays that measure the expression of Nrf2 target genes and assess the cellular response to oxidative stress. We also help clients measure key biomarkers of oxidative stress and inflammation. Using techniques such as ELISA, Western blotting, and flow cytometry, we can quantify the activity of Nrf2 in response to the drug. We provide assessment parameters such as cell viability, proliferation, and senescence-associated beta-galactosidase activity to help clients evaluate drug efficacy. Our suite of services provides a comprehensive understanding of the functional effects of Nrf2 modulation.
Anti-Aging Drugs Targeting Nrf2 in Aging-Related Neurodegenerative Diseases
Neurodegenerative diseases such as Alzheimer's and Parkinson's are closely associated with the aging process. CD BioSciences is developing anti-aging drugs targeting Nrf2 in these diseases.
- Alzheimer's disease. We help clients study how Nrf2 activators reduce amyloid-beta accumulation and tau phosphorylation, two hallmarks of Alzheimer's disease.
- Parkinson's disease. Oxidative stress leads to the degeneration of dopaminergic neurons in Parkinson's disease. We assist clients in analyzing the effects of Nrf2 activators on neuroprotection by upregulating the expression of antioxidant enzymes that may help mitigate neurotoxicity.
The development of anti-aging drugs targeting Nrf2 represents a promising strategy in the fight against aging and age-related neurodegenerative diseases. CD BioSciences aims to help clients develop anti-aging drugs that enhance Nrf2 activity using a comprehensive approach, from initial screening to preclinical development. If you are interested in our services, please feel free to contact us or make an online inquiry.
References
- Brackhan M, et al. Aging, NRF2, and TAU: A Perfect Match for Neurodegeneration? Antioxidants (Basel), 2023, 12 (8): 1564.
- Bruns DR, et al. Nrf2 Signaling and the Slowed Aging Phenotype: Evidence from Long-Lived Models. Oxid Med Cell Longev, 2015, 732596.
- Zinovkin RA, et al. Does Nrf2 Play a Role of a Master Regulator of Mammalian Aging? Biochemistry (Mosc), 2022, 87 (12): 1465-1476.
- Matsumaru D, Motohashi H. The KEAP1-NRF2 System in Healthy Aging and Longevity. Antioxidants (Basel), 2021, 10 (12): 1929.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.
