构建包含tau驱动的记忆丧失不良结局途径(AOP429)的不良结局途径(AOP)网络。
Building a Network of Adverse Outcome Pathways (AOPs) Incorporating the Tau-Driven AOP Toward Memory Loss (AOP429).
作者信息
Tsamou Maria, Roggen Erwin L
机构信息
ToxGenSolutions (TGS), Maastricht, The Netherlands.
出版信息
J Alzheimers Dis Rep. 2022 Jun 7;6(1):271-296. doi: 10.3233/ADR-220015. eCollection 2022.
The adverse outcome pathway (AOP) concept was first proposed as a tool for chemical hazard assessment facilitating the regulatory decision-making in toxicology and was more recently recommended during the BioMed21 workshops as a tool for the characterization of crucial endpoints in the human disease development. This AOP framework represents mechanistically based approaches using existing data, more realistic and relevant to human biological systems. In principle, AOPs are described by molecular initiating events (MIEs) which induce key events (KEs) leading to adverse outcomes (AOs). In addition to the individual AOPs, the network of AOPs has been also suggested to beneficially support the understanding and prediction of adverse effects in risk assessment. The AOP-based networks can capture the complexity of biological systems described by different AOPs, in which multiple AOs diverge from a single MIE or multiple MIEs trigger a cascade of KEs that converge to a single AO. Here, an AOP network incorporating a recently proposed tau-driven AOP toward memory loss (AOP429) related to sporadic (late-onset) Alzheimer's disease is constructed. This proposed AOP network is an attempt to extract useful information for better comprehending the interactions among existing mechanistic data linked to memory loss as an early phase of sporadic Alzheimer's disease pathology.
不良结局途径(AOP)概念最初是作为一种化学危害评估工具提出的,有助于毒理学中的监管决策,最近在BioMed21研讨会上被推荐为一种用于表征人类疾病发展中关键终点的工具。这种AOP框架代表了基于机制的方法,使用现有数据,对人类生物系统更现实且相关。原则上,AOP由分子引发事件(MIE)描述,这些事件会引发导致不良结局(AO)的关键事件(KE)。除了单个AOP外,AOP网络也被认为有助于支持风险评估中对不良反应的理解和预测。基于AOP的网络可以捕捉不同AOP所描述的生物系统的复杂性,其中多个AO从单个MIE发散,或者多个MIE触发一系列KE,这些KE汇聚到单个AO。在此,构建了一个AOP网络,该网络纳入了最近提出的与散发性(晚发性)阿尔茨海默病相关的tau驱动的记忆丧失AOP(AOP429)。这个提议的AOP网络旨在提取有用信息,以便更好地理解与散发性阿尔茨海默病病理学早期阶段记忆丧失相关的现有机制数据之间的相互作用。
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