Fu Yongyao, Zhao Deming, Pan Bo, Wang Jihong, Cui Yongyong, Shi Fushan, Wang Chunyu, Yin Xiaoming, Zhou Xiangmei, Yang Lifeng
State Key Laboratories for Agrobiotechnology, Key Lab of Animal Epidemiology and Zoonosis, Ministry of Agriculture, National Animal Transmissible Spongiform Encephalopathy Laboratory, College of Veterinary Medicine, China Agricultural University, Beijing, China.
Division of Basic Biomedical Sciences, Sanford School of Medicine of the University of South Dakota, Vermillion, South Dakota, USA.
J Alzheimers Dis. 2015;47(4):915-26. doi: 10.3233/JAD-150312.
Alzheimer's disease (AD) is the most common cause of dementia. Mice in the transgenic AβPPswe/PS1dE9 mouse line express a chimeric mouse/human amyloid-β protein precursor (Mo/HuAβPP695swe) and mutant human presenilin 1 (PS1-dE9) associated with early-onset AD. Knowing the protein expression in these mice may offer better understanding of the pathological changes in AD. In this study, we used two-dimensional gel electrophoresis combined with mass spectrometry techniques to compare protein expression in AβPPswe/PS1dE9 mice with age-matched wild-type mice throughout the disease progression. We identified 15 proteins that were significantly different between the AβPPswe/PS1dE9 mice and age-matched controls and also changed with disease development. Among those, the expression levels of the following proteins in AβPPswe/PS1dE9 mice were at least 1.5 times higher than those in normal mice: DCC-interacting protein 13-beta, serum albumin, creatine kinase B-type, heat shock 70 kDa protein 1A, T-complex protein 1 subunit beta, adenylate kinase isoenzyme 1, pyruvate dehydrogenase E1 component subunit beta mitochondrial, and V-type proton ATPase catalytic subunit A. Levels of the following proteins in AβPPswe/PS1dE9 mice were at least 1.5 times lower than those in normal mice: dihydropyrimidinase-related protein 2, actin cytoplasmic 2, isoform 1 of V-type proton ATPase catalytic subunit, tubulin alpha-1C chain, F-actin-capping protein subunit alpha-2, ubiquitin carboxyl-terminal hydrolase isozyme L1, and actin cytoplasmic 1. These proteins are involved in regulating various cellular functions, including cytoskeletal structure, energy metabolism, synaptic components, and protein degradation. These findings indicate altered protein expression in the pathogenesis of AD and illuminate novel therapeutic avenues for treatment in AD.
阿尔茨海默病（AD）是痴呆最常见的病因。转基因AβPPswe/PS1dE9小鼠品系中的小鼠表达一种嵌合的小鼠/人类淀粉样β蛋白前体（Mo/HuAβPP695swe）和与早发性AD相关的突变型人类早老素1（PS1-dE9）。了解这些小鼠中的蛋白质表达情况可能有助于更好地理解AD的病理变化。在本研究中，我们使用二维凝胶电泳结合质谱技术，在整个疾病进展过程中比较AβPPswe/PS1dE9小鼠与年龄匹配的野生型小鼠的蛋白质表达。我们鉴定出15种在AβPPswe/PS1dE9小鼠与年龄匹配的对照之间存在显著差异且随疾病发展而变化的蛋白质。其中，AβPPswe/PS1dE9小鼠中以下蛋白质的表达水平比正常小鼠高至少1.5倍：DCC相互作用蛋白13-β、血清白蛋白、肌酸激酶B型、热休克70 kDa蛋白1A、T复合物蛋白1亚基β、腺苷酸激酶同工酶1、线粒体丙酮酸脱氢酶E1组分亚基β以及V型质子ATP酶催化亚基A。AβPPswe/PS1dE9小鼠中以下蛋白质的水平比正常小鼠低至少1.5倍：二氢嘧啶酶相关蛋白2、胞质肌动蛋白2、V型质子ATP酶催化亚基同工型1、微管蛋白α-1C链、F-肌动蛋白封端蛋白亚基α-2、泛素羧基末端水解酶同工酶L1以及胞质肌动蛋白1。这些蛋白质参与调节各种细胞功能，包括细胞骨架结构、能量代谢、突触成分和蛋白质降解。这些发现表明AD发病机制中存在蛋白质表达改变，并为AD治疗开辟了新的治疗途径。
