Open AccessDab2 attenuates brain injury in APP/PS1 mice via targeting transforming growth factor-beta/SMAD signaling
Author(s) -
Lei Song,
Yue Gu,
Jing Jie,
Xiaoxue Bai,
YingWei Yang,
Chaoying Liu,
Qun Li
Publication year - 2014
Publication title -
neural regeneration research/neural regeneration research
Language(s) - Uncategorized
Resource type - Journals
SCImago Journal Rank - 0.93
H-Index - 38
eISSN - 1876-7958
pISSN - 1673-5374
DOI - 10.4103/1673-5374.125328
Subject(s) - smad , neuroprotection , transforming growth factor , signal transduction , transforming growth factor beta , hippocampal formation , microbiology and biotechnology , cancer research , microglia , biology , medicine , endocrinology , inflammation
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.