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Authors & Affiliations
Matteo Barel, Georg Winter, Nuno Maulide, Gaia Novarino
Abstract
Metabolism actively interacts with the proteome, transcriptome, and genome, thereby influencing all facets of biological information and providing cells the adaptability required for optimal functioning across time and space. Neurodevelopment, in particular, depends on the timely integration of numerous molecular signals across cell types, thus deeply relying on metabolite signaling functions. Although measuring changes in metabolites is useful to describe the association between molecules and disorders, the molecular mechanisms through which these metabolites affect neurodevelopment remain unknown. The regulation of protein function by metabolites has previously been described as a key process to maintain and modulate cell physiology and plays a vital role in the organism's development, adaptation, and survival. However, the study of protein-metabolite interactions (PMIs) is still fragmentary and largely unexplored. We aim to understand if PMIs influence neurodevelopment and neurodevelopmental disorders. We analyzed the metabolome of the wild-type mouse cerebral cortex obtained at three different time points: embryonic day 14.5 (E14.5), postnatal day 2 (P2), and postnatal day 40 (P40). We selected different metabolites whose levels change during development and have distinct chemical properties. In particular, we intend to (1) define the proteins that interact with specific metabolites in neurons, (2) characterize PMIs and unravel new molecular mechanisms central to neurodevelopmental processes, (3) determine which cellular phenotypes are affected if specific PMIs are altered. Unraveling and characterizing PMIs is essential not only to explain the molecular basis of neurodevelopmental disorders but also to potentially modulate specific biological pathways as therapeutic intervention.