Alizarin attenuates oxidative stress-induced mitochondrial damage in vascular dementia rats by promoting TRPM2 ubiquitination and proteasomal degradation via Smurf2.

BACKGROUND

Alizarin (AZ) is a natural anthraquinone with anti-inflammatory and moderate antioxidant properties.

PURPOSE

In this study, we characterized the role of AZ in a rat model of vascular dementia (VaD) and explored its underlying mechanisms.

METHODS

VaD was induced by bilateral common carotid artery occlusion.

RESULTS

We found that AZ attenuated oxidative stress and improved mitochondrial structure and function in VaD rats, which led to the improvement of their learning and memory function. Mechanistically, AZ reduced transient receptor potential melastatin 2 (TRPM2) expression and activation of the Janus-kinase and signal transducer activator of transcription (JAK-STAT) pathway in VaD rats. In particular, the reduction in the expression of TRPM2 channels was the key to the attenuation of the oxidative stress-induced mitochondrial damage, which may be achieved by increasing the expression of the E3 ubiquitin ligase, Smad-ubiquitination regulatory factor 2 (Smurf2); thereby increasing the ubiquitination and degradation levels of TRPM2.

CONCLUSION

Our results suggest that AZ is an effective candidate drug for ameliorating VaD and provide new insights into the current clinical treatment of VaD.