NAD⁺ modulates REST isoform expression and its downstream mitophagy in Alzheimer's disease.

Authors

Maria J Lagartos-Donate, Beatriz Escobar-Doncel, Caroline Shi-Qi Zhang, Evandro Fei Fang

Published in

Autophagy. Jul 09, 2026. Epub Jul 09, 2026.

Abstract

Repressor Element 1-Silencing Transcription factor (REST) emerges as a metabolism-sensitive transcriptional hub that supports basal mitophagy, mitochondrial quality, and synaptic function in neurons. In Alzheimer's disease, REST becomes mislocalized and functionally impaired, coinciding with early defects in mitochondrial quality control. Activation of the NAD⁺ -SIRT1 axis enhances REST nuclear activity, restores its mitochondrial and neuroprotective gene programs, and attenuates pathological and cognitive decline in experimental AD models. Our study highlights REST as a promising target to preserve mitochondrial and neuronal function.Abbreviations:Alzheimer's disease, AD; Repressor Element 1-Silencing Transcription factor, REST; Nicotinamide Adenine Dinucleotide, NAD⁺.

PMID:
42423068
Bibliographic data and abstract were imported from PubMed on 09 Jul 2026.

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