Article: SARM1 Enzyme Drives Axonal NAD+ Loss and Degeneration: Preclinical Findings

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Neurological Health Preclinical

SARM1 Enzyme Drives Axonal NAD+ Loss and Degeneration: Preclinical Findings

Synopsis

Axonal degeneration, or the breakdown of nerve fibers, happens early in many neurological diseases. The protein SARM1 is a key driver of this process, causing axons to lose NAD+, a vital molecule for energy and cell health. This study found that the TIR part of SARM1 can directly break down NAD+ into ADP-ribose, cyclic ADP-ribose, and nicotinamide, with nicotinamide acting as a natural brake on the enzyme. Experiments using injured neurons showed that SARM1’s ability to break down NAD+ is necessary for axon loss after damage. These findings highlight SARM1 as a potential target for therapies aimed at protecting axons in neurological disorders, and reveal that TIR domains, commonly studied protein motifs, can have enzymatic activity.

Journal

Neuron

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