Programmed neurite degeneration in human central nervous system neurons driven by changes in NAD⁺ metabolism.

ABSTRACT: Neurite degeneration (ND) precedes cell death in many neurodegenerative diseases. However, it remains unclear how this compartmentalized cell death process is orchestrated in the central nervous system (CNS). The establishment of a CNS axotomy model (using modified 3D LUHMES cultures) allowed us to study metabolic control of ND in human midbrain-derived neurons without the use of toxicants or other direct disturbance of cellular metabolism. Axotomy lead to a loss of the NAD⁺ synthesis enzyme NMNAT2 within 2 h and a depletion of NAD⁺ within 4-6 h. This process appeared specific, as isolated neurites maintained ATP levels and a coupled mitochondrial respiration for at least 6 h. In the peripheral nervous system (PNS) many studies observed that NAD⁺ metabolism

SUBMITTER: Brull M 

PROVIDER: S-EPMC11742042 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature