Prof. Lukas Neukomm, Universität Lausanne

Nicotinamide adenine dinucleotide (NAD⁺) metabolism is essential for neurons; its dysregulation contributes to several neurodegenerative diseases and serves as a critical driver of axon degeneration. The NAD⁺ precursor nicotinamide mononucleotide (NMN) and its vitamin B3 derivatives—commonly known as niacin–are widely used as dietary supplements to enhance NAD⁺. NMN acts as a substrate for NAD⁺ synthesis, promoting healthy aging and longevity. Surprisingly, NMN also has a pro-degenerative role, as its accumulation leads to axon and neurodegeneration. Thus, NMN resides at the intersection of healthy aging, longevity, and axon/neurodegeneration. In the Neukomm lab, we utilize Drosophila to gain insights into the endogenous synthesis of NMN, its exogenous supply, and its regulation in axons and neurons. We combine advanced genetics with metabolic and molecular approaches, employing sparsely labeled neurons and their axons along with automated behavioral analyses. We will demonstrate how elevated NMN drives axon degeneration by activating an evolutionarily conserved programmed axon degeneration pathway and how NMN also contributes to neurodegeneration. Our latest insights into axonal and neuronal NMN homeostasis in the fly may provide novel targets for therapeutic interventions in mammals.