La deficiencia neurodegenerativa de NMNAT2 promueve el procesamiento de APP de manera dependiente de SARM1

glycolytic impairment followed by deficits in mitochondrial respiration. Knockdown of the NAD+ hydrolase sterile alpha and TIR motif-containing protein 1 (SARM1) restores mitochondrial function and normalizes APP-CTF levels in NMNAT2 knockout neurons, whereas NAD+ supplementation provides only modest rescue. Together, these data demonstrate that neuronal NAD+ depletion drives progressive, SARM1-dependent disruption of glucose metabolism and proteostasis, impairing APP processing. The NMNAT2-SARM1 axis thus links metabolic stress to proteinopathy and highlights SARM1 as a central mediator of neurodegenerative