Dab2 attenuates brain injury in APP/PS1 mice via targeting transforming growth factor-beta/SMAD signaling

Transforming growth factor-beta (TGF-beta) type II receptor (T beta 3RII) levels are extremely low in the brain tissue of patients with Alzheimer's disease. This receptor inhibits TGF-beta 1/SMAD signaling and thereby aggravates amyolid-beta deposition and neuronal injury. Dab2, a specific adapter protein, protects T RII from degradation and ensures the effective conduction of TGF-beta 1/SMAD signaling. In this study, we used an adenoviral vector to overexpress the Dab2 gene in the mouse hippo campus and investigated the regulatory effect of Dab2 protein on TGF-beta 1/SMAD signaling in a mouse model of Alzheimer's disease, and the potential neuroprotective effect. The results showed that the T beta RII level was lower.in APP/PS1 mouse hippocampus than in normal mouse hippocampus. After Dab2 expression, hippocampal T beta RII and p-SMAD2/3 levels were significantly increased, while amyloid-beta deposition, microglia activation, tumor necrosis factor-and interleulin-6 levels and neuronal loss were significantly attenuated in APP/PS1 mouse brain tissue. These results suggest that Dab2 can exhibit neuroprotective effects in Alzheimer's disease by regulating TGF-beta 1/SMAD signaling.