Bridging brain insulin resistance to Alzheimer’s pathogenesis
Brain insulin resistance (BIR) links type 2 diabetes mellitus (T2DM) and Alzheimer’s disease. Abnormal biliverdin reductase-A (BVR-A) levels were observed in both T2D and AD and were associated with insulin resistance.
The researchers show that reduced BVR-A levels alter insulin signaling and mitochondrial bioenergetics in the brain. The authors also demonstrate that BVR-A is required to shuttle glycogen synthase kinase 3β (GSK3β) into the mitochondria.
Reduced biliverdin reductase-A (BVR-A) also impairs pGSK3β phosphorylation impairs oxidative phosphorylation and fosters the activation of the mitochondrial Unfolded Protein Response (UPRmt), causing mitochondrial dysfunction and exacerbating brain insulin resistance in the progression of both T2DM and AD.
https://www.sciencedirect.com/science/article/pii/S221323172400199X
