|Sponsor||Horizon Europe Framework Programme|
|Institution||German Center for Neurodegenerative Diseases|
|Principal investigator||Michela Deleidi
Associated cell lines
Nicotinamide adenine dinucleotide (NAD+) is a central redox cofactor and the limiting substrate of key metabolic enzymes that include the sirtuin family of protein deacylases, the poly(ADP-ribose) polymerases (PARPs) and the cyclic ADP-ribose (cADPr) synthases. Primary deficiencies of NAD+ homeostasis are the result of impaired biosynthesis, while secondary deficiencies can arise due to other factors affecting NAD+ homeostasis, such as increased NAD+ consumption or dietary deficiency of its vitamin B3 precursors. NAD+ depletion can manifest in a wide variety of pathological phenotypes, ranging from rare inherited defects to more common multifactorial, often age-related, diseases. In this project, we will investigate 1) how NAD+ homeostasis is regulated at different stages in life, (2) how its imbalance leads to disease at a systemic level and (3) which NAD+ repletion strategy is the most suitable to prevent or treat specific diseases.