PUBLICATION
Troglitazone as a Novel Nrf2 Activator to Attenuate Oxidative Stress and Exert Neuroprotection
- Authors
- Zhang, L., Wang, S., Zhang, Y., Zhang, X., Xi, J., Wu, J., Fang, J., Zhao, H., Zhang, B.
- ID
- ZDB-PUB-250327-10
- Date
- 2025
- Source
- ACS Chemical Neuroscience : (Journal)
- Registered Authors
- Keywords
- 6-hydroxydopamine, Nrf2, Parkinson’s disease, neuroprotection, troglitazone
- MeSH Terms
-
- Neuroprotection*/drug effects
- Rats
- Humans
- Neuroprotective Agents*/pharmacology
- Oxidative Stress*/drug effects
- NF-E2-Related Factor 2*/metabolism
- Animals
- PC12 Cells
- Kelch-Like ECH-Associated Protein 1/metabolism
- Zebrafish
- Troglitazone*/pharmacology
- Oxidopamine
- PubMed
- 40135498 Full text @ ACS Chem. Neurosci.
Citation
Zhang, L., Wang, S., Zhang, Y., Zhang, X., Xi, J., Wu, J., Fang, J., Zhao, H., Zhang, B. (2025) Troglitazone as a Novel Nrf2 Activator to Attenuate Oxidative Stress and Exert Neuroprotection. ACS Chemical Neuroscience. :.
Abstract
Nuclear factor erythroid 2 related factor 2 (Nrf2) is closely associated with neurodegenerative diseases, and the Nrf2-mediated activation of antioxidant response elements (AREs) brings about validated strategies for treating neurodegenerative diseases. Here, we discovered that troglitazone, a clinical medication for diabetes mellitus, could serve as a Nrf2 activator to rescue neuronal damages both in vitro and in vivo. The mechanism of troglitazone action involves binding with kelch-like ECH-associated protein 1 (Keap1) and the activation of Nrf2. This process leads to the migration of Nrf2 to the cell nucleus and transactivates the AREs. Troglitazone exhibits significant alleviation of oxidative stress in PC12 cells induced by hydrogen peroxide or 6-hydroxydopamine (6-OHDA). In vivo studies indicate that troglitazone could rescue the motor activity and neurodevelopmental deficiency in zebrafish induced by 6-OHDA. Additionally, mass spectrometry imaging demonstrates that troglitazone could cross the zebrafish blood-brain barrier, supporting the application of troglitazone in treating neurodegenerative diseases. Overall, this work reveals that the novel Nrf2 activator troglitazone has potential therapeutic value for neurodegeneration and provides a foundation for its repurposing.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping