title: Dab2 attenuates brain injury in APP/PS1 mice via targeting transforming growth factor-beta/SMAD signaling.
abstract: Transforming growth factor-beta (TGF-β) type II receptor (TβRII) levels are extremely low in the brain tissue of patients with Alzheimer's disease. This receptor inhibits TGF-β1/SMAD signaling and thereby aggravates amyolid-beta deposition and neuronal injury. Dab2, a specific adapter protein, protects TβRII from degradation and ensures the effective conduction of TGF-β1/SMAD signaling. In this study, we used an adenoviral vector to overexpress the Dab2 gene in the mouse hippocampus and investigated the regulatory effect of Dab2 protein on TGF-β1/SMAD signaling in a mouse model of Alzheimer's disease, and the potential neuroprotective effect. The results showed that the TβRII level was lower in APP/PS1 mouse hippocampus than in normal mouse hippocampus. After Dab2 expression, hippocampal TβRII and p-SMAD2/3 levels were significantly increased, while amyloid-beta deposition, microglia activation, tumor necrosis factor-α 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-β1/SMAD signaling.
authors.affiliation: Department of Neurology, Norman Bethune First Hospital of Jilin University, Changchun, Jilin Province, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Song
authors.affiliation: Department of Respiratory Medicine, Norman Bethune First Hospital of Jilin University, Changchun, Jilin Province, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Gu
authors.affiliation: Department of Respiratory Medicine, Norman Bethune First Hospital of Jilin University, Changchun, Jilin Province, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Jie
authors.affiliation: Department of Respiratory Medicine, Norman Bethune First Hospital of Jilin University, Changchun, Jilin Province, China.
authors.forename: Xiaoxue
authors.initials: X
authors.lastname: Bai
authors.affiliation: Department of Respiratory Medicine, Norman Bethune First Hospital of Jilin University, Changchun, Jilin Province, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Respiratory Medicine, Norman Bethune First Hospital of Jilin University, Changchun, Jilin Province, China.
authors.forename: Chaoying
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Neurology, Norman Bethune First Hospital of Jilin University, Changchun, Jilin Province, China.
authors.forename: Qun
authors.initials: Q
authors.lastname: Liu
keywords: Alzheimer's disease; Dab2; SMAD2; SMAD3; amyolid-beta; microglia; nerve regeneration; neural regeneration; neuron; transforming growth factor-β1