NAD + supplementation reduces neuroinflammation and cell senescence in a transgenic mouse model of Alzheimer’s disease via cGAS–STING

Sep 9, 2021Proceedings of the National Academy of Sciences of the United States of America

NAD+ supplements reduce brain inflammation and cell aging in a mouse model of Alzheimer's through the cGAS-STING pathway

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Abstract

Nicotinamide riboside (NR) treatment for 5 months increased brain NAD levels and reduced inflammation in APP/PS1 mutant mice with Alzheimer's disease.

  • NAD levels were found to be reduced, while inflammation markers were increased in the brains of APP/PS1 mutant mice.
  • NR treatment decreased the expression of proinflammatory cytokines and reduced the activation of microglia and astrocytes.
  • The treatment also lowered NLRP3 inflammasome expression, DNA damage, apoptosis, and cellular senescence in the affected brains.
  • cGAS-STING activation, associated with DNA damage and senescence, was elevated in AD mice and normalized by NR treatment.
  • Cell culture experiments indicated that NR's beneficial effects may involve a cGAS-STING-dependent pathway.
  • Increased levels of ectopic DNA were observed in APP/PS1 mutant mice and human AD fibroblasts, which were down-regulated by NR.

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