Novas Abordagens Metodológicas para Avaliar o Risco de Neurodegeneração pela Exposição a Misturas de Contaminantes Alimentares

The neuroNAMix project addresses important challenges associated with ND diseases and their relationship with the food exposome. This initiative intends to prioritise FCs based on their potential neurotoxicity, investigating their cellular effects on an AOP of NT in cell and barriers interconnecting the gut and brain, and provide alternative risk assessment methodologies. Ultimately, the project seeks to contribute to the development of safer food practices, promoting a toxic-free environment and fostering regulatory policies to protect human health. The main objectives and correspondent challenges addressed are as follows: > Prioritization of Food Contaminants according to their potential NT: To prioritise a list of 100 prevalent FCs based on their capacity to cross the intestinal and brain-blood barriers (BBB), addressing the challenge posed by the multiplicity of molecules and the continuous emergence of new FCs and the complexity of chemical mixtures in food. > Investigate the isolated and combined effects on a NT AOP of cells and barriers interconnecting the gut and brain: To investigate the isolated and combined effects of 5 prioritised FCs on neurotoxicity pathways and the very relevant intestinal and BBB integrity, addressing the challenge of understanding the mechanisms by which FCs contribute to neurodegenerative diseases. > Evaluation of the New Approach Methodology proposed: To evaluate the suitability and effectiveness of the developed NAM according to fit-for-purpose indicators. This addresses the challenge of transitioning away from traditional animal studies and adopting alternative high-throughput solutions for risk assessment. > Assessment of Dietary Intake Risk: To assess the dietary intake risk of neurotoxicity from the 5 FCs, and their mixture effects, providing valuable data to inform regulatory policies and public health interventions aimed at reducing exposure in the food supply. In this way, neuroNAMix addresses the challenge of raising consumers' awareness about the neurotoxic effects of FCs, in an informative and non-alarming manner. neuroNAMix will contribute to pushing the boundaries of current scientific knowledge and practices through its: > Innovative methodologies: By integrating a NAM comprising cells and barriers within the gut-brain connection, the project adopts innovative approaches to assess NT. This method involves a complex and interconnected group of cells and epithelial barriers, mimicking body physiology and overcoming the limitations of traditional animal studies. It enables the assessment of a broader range of toxicants, thereby enhancing the efficiency of risk assessment. > Comprehensive approach: neuroNAMix considers FC and FCx (FC mixtures) effects on cellular NT as well as in barriers integrity together with dietary intake risk. This holistic approach goes beyond traditional methods, which often focus solely on individual compounds or limited aspects of NT. > A consumer interface to evaluate the NT risk from dietary exposure: The development of a practical and user-friendly consumer interface tool for tailored assessment and mitigation of NT risks, neuroNAMix goes beyond traditional risk assessment often designed for regulatory or industry use and may not be easily accessible or understandable for consumers.