The impact of Apolipoprotein E in heavy metal mixtures toxicity–a mechanistic approach for neurological disease prevention-ApoEMETOX
Nr.crt. 114TE/2025
Project manager: DOCEA ANCA OANA
Time 01.08.2025-31.07.2027
Neurodevelopmental disorders have a huge impact on society and the environment can influence the causal chain between a genetic predisposition and neurodevelopmental disease or influence the severity of these diseases. Heavy metals as cadmium, mercury, arsenic and lead alone or as a mixture frequently found in the environment remains a major health concern, especially for the developing central nervous system. Genetic modifiers of vulnerability to heavy metals may exert their influence during both development and adulthood, but the molecular mechanisms have yet to be fully delineated. Apolipoprotein E (APOE) appears to play a key role in susceptibility to heavy metal toxicity, with evidence that variants of APOE can influence the toxicodynamics and toxicokinetics of MeHg, without evidence for other heavy metals/mixtures and a proof mechanism for these effects. ApoEMETOX includes a mechanistic approach to study the heavy metals-neurotoxicity modulation by ApoE during neurodevelopment. C. elegans model will be used to assess the relationship and to understand the underlying cellular mechanisms of mixture neurotoxicity compared with a single compound. There are 2 main objectives in ApoEMETOX:
- Determine whether ApoE isoforms modulate single/mixture heavy metals toxicity;
- Investigate the underlying molecular mechanism. The unique knowledge originating from this broad approach will lead to translational products such as early diagnosis tools or prevention strategies.
Our team:
Anca Oana Docea-Project manager
Andrei Biță-Postdoctoral Fellow
Antonia Radu-Postdoctoral Fellow
Cătălin Bogdan-Research Fellow
Liliana Cercelaru-Research Fellow
Stage 1-Gathering information regarding real life exposure scenarios, Generation of transgenic C. elegans strains and Dissemination and exploitation
Act. 1.1-Gathering information regarding real life exposure scenarios
Act. 1.2-Generation of transgenic C. elegans strains to investigate whether the presence of ApoE alleles modulated heavy metal-induced neurotoxicity
Act.1.3-Generating of transgenic C. elegans strains to investigate the molecular mechanism of ApoE in mediating heavy metal toxicity in C. elegans
Act.1.4-Dissemination and exploitation
Stage 2- Gathering information regarding real life exposure scenarios – continuation
Generation of transgenic C. elegans strains- continuation
Determining whether the presence of ApoE alleles modulates heavy metal-induced neurotoxicity in C. elegans
Investigating the molecular mechanism of ApoE in mediating heavy metal toxicity in C. elegans
Data analysis and interpretation
Dissemination and exploitation-continuation
Act.2.1-Gathering information regarding real life exposure scenarios – continuation
Act.2.2-Generation of transgenic C. elegans strains to investigate whether the presence of ApoE alleles modulated heavy metal-induced neurotoxicity- continuation
Act.2.3-Generating of transgenic C. elegans strains to investigate the molecular mechanism of ApoE in mediating heavy metal toxicity in C. elegans – continuation
Act.2.4-Determining whether the presence of ApoE alleles modulates heavy metal-induced neurotoxicity in C. elegans: Heavy metal exposure(WP3)
Act.2.5-Determination of heavy metal content:Hg,Pb,As,Cd
Act.2.6-DAergic Neurodegeneration
Act.2.7-Cholinergic Neurodegeneration
Act.2.8-General Behaviors
Act.2.9-DAergic-Dependent Behavior
Act.2.10-CHOergic-dependent behaviors
Act.2.11-Investigate the molecular mechanism of ApoEs in mediating heavy metals toxicity in C. elegans (WP4)
Act.2.12-Lethality analysis
Act.2.13-Measurement of isoprostanes (F-3 IsoPs), ATP depletion
Act.2.14-Mitochondrial membrane potential
Act.2.15-Oxidative stress response regulated by Nrf-2/SKN-1 pathway
Act.2.16-Data analysis and interpretation
Act.2.17-Dissemination and exploitation-continuation