Neural Regeneration Research ›› 2014, Vol. 9 ›› Issue (1): 41-50.doi: 10.4103/1673-5374.125328

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

Lei Song1, Yue Gu2, Jing Jie2, Xiaoxue Bai2, Ying Yang2, Chaoying Liu2, Qun Liu1   

  1. 1 Department of Neurology, Norman Bethune First Hospital of Jilin University, Changchun, Jilin Province, China
    2 Department of Respiratory Medicine, Norman Bethune First Hospital of Jilin University, Changchun, Jilin Province, China
  • Received:2013-11-29 Online:2014-01-05 Published:2014-01-05
  • Contact: Qun Liu, M.D., Department of Neurology, Norman Bethune First Hospital of Jilin University, Changchun 130021, Jilin Province, China, songleisl@163.com. Chaoying Liu, Department of Respiratory Medicine, Norman Bethune First Hospital of Jilin University, Changchun, Jilin Province, China, 48580116@qq.com.

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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.

Key words: nerve regeneration, transforming growth factor-β1, Dab2, Alzheimer’s disease, amyolid-beta, neuron, SMAD2, SMAD3, microglia, neural regeneration