Loss of REST associated with Alzheimer's disease pathology is ameliorated by NAD+ - Summary - MDSpire

Loss of REST associated with Alzheimer's disease pathology is ameliorated by NAD+

  • By

  • Maria J Lagartos-Donate

  • Beatriz Escobar-Doncel

  • Shi-qi Zhang

  • Jun-ping Pan

  • Noemí Villaseca González

  • Alexander Anisimov

  • Nicola P Montaldo

  • Vidar Jensen

  • Lipeng Mao

  • Bailei Li

  • Nuria Banzon-Pereira

  • Liu Shi

  • Shu-qin Cao

  • Domenica Caponio

  • Pingjie Wang

  • Rajeevkumar Raveendran Nair

  • Oscar Junhong Luo

  • Guobing Chen

  • Alejo J Nevado-Holgado

  • Noel Buckley

  • Hilde Loge Nilsen

  • Evandro Fei Fang

  • February 19, 2026

  • 0 min

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Objective:

To investigate the relationship between REST expression and Alzheimer's disease (AD) pathology, and to explore the potential therapeutic effects of NAD+ on REST levels and AD outcomes.

Key Findings:
  • REST expression and localization changes contribute to AD pathology, highlighting its role in disease progression.
  • Overexpression of REST significantly improves cognitive function and reduces amyloid-β and phosphorylated Tau levels, indicating its protective effects.
  • The NAD+/SIRT1 axis regulates REST expression, impacting mitophagy and synaptic function, suggesting a pathway for therapeutic intervention.
Interpretation:

The findings suggest that targeting REST through NAD+ supplementation may offer a novel therapeutic strategy for AD, potentially restoring mitochondrial function and mitigating neurodegeneration.

Limitations:
  • The study primarily focuses on animal models, which may not fully replicate human AD pathology.
  • Further research is needed to elucidate the precise molecular mechanisms linking NAD+, REST, and AD.
  • Clinical trials are necessary to validate the therapeutic potential of NAD+ in human subjects.
Conclusion:

REST is identified as a promising therapeutic target in AD, with NAD+ playing a crucial role in its regulation and potential neuroprotective effects.

Original Source(s)

Loss of REST associated with Alzheimer's disease pathology is ameliorated by NAD+

  • by Maria J Lagartos-Donate, Beatriz Escobar-Doncel, Shi-qi Zhang, Jun-ping Pan, Noemí Villaseca González, Alexander Anisimov, Nicola P Montaldo, Vidar Jensen, Lipeng Mao, Bailei Li, Nuria Banzon-Pereira, Liu Shi, Shu-qin Cao, Domenica Caponio, Pingjie Wang, Rajeevkumar Raveendran Nair, Oscar Junhong Luo, Guobing Chen, Alejo J Nevado-Holgado, Noel Buckley, Hilde Loge Nilsen, Evandro Fei Fang

  • February 19, 2026

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