NMNAT2 supports vesicular glycolysis via NAD homeostasis to fuel fast axonal transport.

ABSTRACT:

Background

Bioenergetic maladaptations and axonopathy are often found in the early stages of neurodegeneration. Nicotinamide adenine dinucleotide (NAD), an essential cofactor for energy metabolism, is mainly synthesized by Nicotinamide mononucleotide adenylyl transferase 2 (NMNAT2) in CNS neurons. NMNAT2 mRNA levels are reduced in the brains of Alzheimer's, Parkinson's, and Huntington's disease. Here we addressed whether NMNAT2 is required for axonal health of cortical glutamatergic neurons, whose long-projecting axons are often vulnerable in neurodegenerative conditions. We also tested if NMNAT2 maintains axonal health by ensuring axonal ATP levels for axonal transport, critical for axonal function.

Methods

We generated mouse and cultured neuron models to determine the impa

SUBMITTER: Yang S 

PROVIDER: S-EPMC10823734 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature