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 speciifc 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 signiif-cantly increased, while amyloid-beta deposition, microglia activation, tumor necrosis factor-βand interleulin-6 levels and neuronal loss were signiifcantly 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.

Dab2调控阿尔茨海默病小鼠模型海马内TGF-β1/SMADs信号传导并减轻其脑损伤

目的 研究Dab2蛋白对阿尔茨海默病疾病模型中TGF-β1/SMADs信号通路的调节作用以及其对阿尔茨海默病小鼠脑损伤的影响.方法 24只APP/PS1双转基因小鼠随机分为AD组、Vector组和Dab2组,每组8只,并将10只阴性对照小鼠作为对照组(Control).对照组不做任何处理;饲养1个月后,AD组小鼠经双侧海马注射生理盐水,Dab2组小鼠双侧海马注射Dab2腺相关病毒质粒,Vector组小鼠双侧海马注射阴性对照质粒.所有小鼠于鼠龄9个月时进行行为学检测.10月龄时处死ELISA法检测脑组织中Aβ含量;Western blot检测海马中Dab2、TβRⅡ和p-SMAD2/3的表达.结果 Dab2腺相关病毒质粒可在小鼠海马内高效表达Dab2.Dab2组小鼠海马组织中TβRⅡ、p-SMAD2和p-SMAD3含量明显高于其阴性对照Vector组.Dab2组小鼠海马内Aβ含量明显低于Vector组,并且行为学评分明显高于Vector组小鼠.结论 Dab2过表达可通过上调TGF-β1/SMADs信号通路的传导,减轻阿尔茨海默病小鼠海马内Aβ的含量并改善其神经功能.

DAB2IP 基因的研究进展

Human DAB2 interaction protein (DAB2IP) is a novel member of Ras GTPase-activating protein family. It interacts directly with disabled-2 protein (DAB2/DOC2) which suppresses growth of cancers derived from different tissues, including mammary, prostate and ovarian cancers. DAB2IP was identified as an immediate downstream effector mediated by DAB2/DOC2. DAB2IP and DAB2/DOC2 form a unique protein complex that has a negative regulatory effect on the Ras-mediated signal pathway. It is demonstrated that DAB2IP is a tumor suppressor gene inactivated by methylation in several cancers. This article reviews the structure and biological functions of DAB2IP gene as well as its potential roles in carcinogenesis and evolution.