Zhou Yuan, Chen Lintao, Zhou Xi, Pei Yechun, Wei Shuangshuang, Mehmood Anum, Xiang Yang K, Wang Dayong
Laboratory of Biotechnology and Molecular Pharmacology, Hainan Key Laboratory of Sustainable Utilization of Tropical Bioresources, Hainan University, Haikou, Hainan 570208, China.
Department of Molecular and Integrative Physiology, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA.
J Appl Bioinforma Comput Biol. 2018;7(3). doi: 10.4172/2329-9533.1000155. Epub 2018 Sep 18.
Alzheimer's disease (AD) is a lifelong progressive neurodegenerativa disease related with accumulation of amyloid β peptide (Aβ) produced by processing of amyloid precursor protein (APP) in the brain. In spite of several-decades effort on AD, there is still no medicine used to intervene with its pathological processes. Our previous studies made in transgenic animal models harboring familial AD genes of mutant presenilin 1 and amyloid precursor protein (APP) showed that βAR gene knock-out (βAR-KO) is beneficial in senile AD animals. Consistently, an epidemiological study lasted for two decades showed that the sole usage of β blockers as antihypertensive medicines is associated with fewer brain lesions and less brain shrinkage seen in senile AD patients. In order to understand why senile βAR-KO AD mice had better learning and memory, genomic effects of βAR-KO in the double transgenic AD mice were investigated. In the analysis, major genomic significance of βAR-KO was directed to influence protein-processing and presentation involving membrane structure and MHC class I and II protein complex, and lysosome and hydrolase activity for protein degradation, which are critical for accumulation of amyloid β peptide, the hallmark of AD.
阿尔茨海默病（AD）是一种与大脑中淀粉样前体蛋白（APP）加工产生的淀粉样β肽（Aβ）积累相关的终身进展性神经退行性疾病。尽管在AD研究上付出了数十年努力，但仍没有用于干预其病理过程的药物。我们之前在携带早老素1和淀粉样前体蛋白（APP）家族性AD基因的转基因动物模型中进行的研究表明，β肾上腺素能受体基因敲除（βAR-KO）对老年AD动物有益。同样，一项持续了二十年的流行病学研究表明，仅使用β受体阻滞剂作为抗高血压药物与老年AD患者较少的脑损伤和较小的脑萎缩有关。为了理解为什么老年βAR-KO AD小鼠具有更好的学习和记忆能力，我们研究了βAR-KO在双转基因AD小鼠中的基因组效应。在分析中，βAR-KO的主要基因组意义在于影响涉及膜结构以及MHC I类和II类蛋白复合物的蛋白质加工和呈递，以及影响用于蛋白质降解的溶酶体和水解酶活性，而这些对于AD的标志——淀粉样β肽的积累至关重要。
