Title : Search for candidate miRNAs implicated in putative Adverse Outcome Pathway (AOP) relevant to sporadic Alzheimer’s disease
Sporadic (late-onset) Alzheimer’s disease (sAD) is a progressive neurodegenerative age-related disease, caused by interaction of genetic and environmental factors, leading to brain damage accompanied by memory loss and cognitive impairment. Up till now, animal-based approaches developed to elucidate the AD-related pathophysiological mechanisms, failed to translate into effective therapeutic treatments or tools for diagnosis. In addition, existing research on AD development is mainly focused on the genetic (familial) type of AD with the most extensively studied AD-related mechanism being, amyloidopathy and tauopathy. The initiating events, needed for detection of early AD pathogenesis, remain elusive. Subsequently, the diagnosis of sAD at early stage is currently poor and inaccurate.
During the last decades, microRNAs (miRNAs) have attracted much attention due to their fundamental role in the modulation of numerous biological processes. Several human miRNAs have been implicated in neurotoxicity and AD development. Systematic literature searches revealed processes shared by neurotoxic compounds and sAD, suggesting that established novel approach methods (NAMs) developed for toxicity testing may provide insight in the early processes of sAD development.
The existing human and animal data, as well as NAMs data were structured using the adverse outcome pathways (AOPs) concept. While developed for toxicology, the AOP concept was proven to be a useful tool for collecting complex biological knowledge on diseases. Proposed AOPs for AD pathogenesis may improve the understanding of the potential chain of events, triggered by molecular initiating events and linked to adverse outcomes. A Tau-driven AOP toward memory loss has been proposed, providing a biologically plausible mechanistic approach by which possible sequential key events are described to be associated with AD pathogenesis. Chemical neurotoxicants have been also suggested as plugs-in for the AOP for memory loss. In addition, the identification of miRNAs functioning these suggested sequential events leading to memory loss may support the discovery of predictive biomarkers commonly dysregulated in both neurotoxicity and AD. Taken together, the existing data of miRNAs may provide an effective approach to understand the mechanisms underlying the AD development, even at early AD stage.
What will audience learn from your presentation?
- A proposed Tau-driven AOP for memory loss
- Environmental induced neurotoxicity and sporadic AD may share common dysregulated processes
- Creating miR-target interaction networks related to pathological processes involved in sporadic AD initiation and progression, and environmental chemical-induced neurotoxicity, may support the understanding of the mechanisms underlying sAD initiation and early progression.