Bilberry anthocyanins attenuate mitochondrial dysfunction via β-catenin/TCF pathway in Alzheimer’s disease

Abstract

Alzheimer’s disease (AD) is a common form of neurodegeneration. In this study, we investigated the modulating effect of bilberry anthocyanins (BAs) on AD-like pathology in the APP/PSEN1 transgenic mouse and then explored the underlying mechanisms using the HT22 cells. We found that BAs significantly reduced the amyloid plaque load and the levels of β-amyloid 1–42 (Aβ42) in the brain and serum of APP/PSEN1 mice. Furthermore, BAs improved mitochondrial morphology and reduced brain NO and ROS levels in the APP/PSEN1 mice. Additional experiments using immortalized HT22 cells showed that BAs protected against Aβ42-induced cytotoxicity by reducing ROS levels and restoring mitochondrial homeostasis, and these effects were partly mediated by upregulation of the mitochondrial homeostasis-related protein Mfn2 via promoting the interaction between β-catenin and TCF7 in nuclear. Together, the results show that BAs have a protective effect against the development of AD, partly through restoration of mitochondrial homeostasis in a β-catenin/TCF-dependent manner.

Keywords

• Alzheimer’s disease
• Bilberry anthocyanins
• β-catenin/TCF signaling pathway
• Mitochondrial dysfunction