Brai Emanuele, Stuart Skye, Badin Antoine-Scott, Greenfield Susan A
Neuro-Bio Ltd., Culham Science CentreAbingdon, United Kingdom.
School of Physiology, Pharmacology and Neuroscience, Faculty of Biomedical Sciences, University of BristolBristol, United Kingdom.
Front Cell Neurosci. 2017 Sep 20;11:291. doi: 10.3389/fncel.2017.00291. eCollection 2017.
Currently there is no widely accepted animal model reproducing the full pathological profile of Alzheimer's disease (AD), since the basic mechanisms of neurodegeneration are still poorly understood. We have proposed that the interaction between the α7 nicotinic acetylcholine receptor (α7-nAChR) and a recently discovered toxic peptide, cleaved from the acetylcholinesterase (AChE) C-terminus, could account for the aberrant processes occurring in AD. In this article we describe a new application on model procedure, which combines the advantages of both and preparations, to study the effects of the AChE-derived peptide on the rat basal forebrain (BF). Western blot analysis showed that the levels of α7-nAChR, p-Tau and Aβ are differentially expressed upon the AChE-peptide administration, in a selective site-dependent manner. In conclusion, this methodology demonstrates the action of a novel peptide in triggering an AD-like phenotype and proposes a new approach for manipulating and monitoring neurochemical processes contributing to neurodegeneration, in a time-dependent and site-specific manner.
目前尚无广泛接受的能够再现阿尔茨海默病（AD）完整病理特征的动物模型，因为神经退行性变的基本机制仍未得到充分理解。我们提出，α7烟碱型乙酰胆碱受体（α7-nAChR）与最近发现的一种从乙酰胆碱酯酶（AChE）C末端切割下来的毒性肽之间的相互作用，可能是AD中发生异常过程的原因。在本文中，我们描述了一种新的模型程序应用，该程序结合了两种制剂的优点，用于研究AChE衍生肽对大鼠基底前脑（BF）的影响。蛋白质免疫印迹分析表明，给予AChE肽后，α7-nAChR、磷酸化tau蛋白（p-Tau）和β淀粉样蛋白（Aβ）的水平以选择性的位点依赖方式差异表达。总之，该方法证明了一种新型肽在触发AD样表型中的作用，并提出了一种新的方法，以时间依赖和位点特异性的方式操纵和监测导致神经退行性变的神经化学过程。
