Building a Network of Adverse Outcome Pathways (AOPs) Incorporating the Tau-Driven AOP Toward Memory Loss (AOP429)

Abstract

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.

An integrative data-centric approach to derivation and characterization of an adverse outcome pathway network for cadmium-induced toxicity

“…Therefore, to assess inorganic cadmium-induced toxicity, it is imperative to construct an AOP network specific to cadmium and its inorganic compounds. Till date, AOP-Wiki has been leveraged to build over 32 different AOP networks for a variety of adverse outcomes such as reproductive disorders [30][31][32][33], neurologic disorders [34][35][36][37], endocrine disorders [25,[38][39][40][41][42][43], developmental disorders [30,40,44,45], hepatic disorders [25,46,47], pulmonary disorders [48][49][50], and others [26,27,[51][52][53][54][55][56][57][58]. Importantly, Chai et al [33] had integrated the data within Comparative Toxicogenomics Database (CTD) [59] and AOP-Wiki to construct an AOP network specific to arsenic-induced reproductive toxicity.…”

An integrative data-centric approach to derivation and characterization of an adverse outcome pathway network for cadmium-induced toxicity

“…Therefore, to assess inorganic cadmium-induced toxicity, it is imperative to construct an AOP network specific to cadmium and its inorganic compounds. Till date, AOP-Wiki has been leveraged to build over 32 different AOP networks for a variety of adverse outcomes such as reproductive disorders [30][31][32][33], neurologic disorders [34][35][36][37], endocrine disorders [25,[38][39][40][41][42][43], developmental disorders [30,40,44,45], hepatic disorders [25,46,47], pulmonary disorders [48][49][50], and others [26,27,[51][52][53][54][55][56][57][58]. Importantly, Chai et al [33] had integrated the data within Comparative Toxicogenomics Database (CTD) [59] and AOP-Wiki to construct an AOP network specific to arsenic-induced reproductive toxicity.…”