Activation of SIRT3 by the NAD+ Precursor Nicotinamide Riboside Protects from Noise-Induced Hearing Loss

作者：Brown, Kevin D.^*; Maqsood, Sadia; Huang, Jing-Yi; Pan, Yong; Harkcom, William; Li, Wei; Sauve, Anthony; Verdin, Eric; Jaffrey, Samie R.

来源：Cell Metabolism, 2014, 20(6): 1059-1068.

DOI：10.1016/j.cmet.2014.11.003

• WALLERIAN DEGENERATION
• AXONAL DEGENERATION
• CALORIE RESTRICTION
• REGENERATION
• INJURY
• GENE
• OVEREXPRESSION
• ACETYLATION
• GLUTATHIONE
• METABOLISM

Intense noise exposure causes hearing loss by inducing degeneration of spiral ganglia neurites that innervate cochlear hair cells. Nicotinamide adenine dinucleotide (NAD(+)) exhibits axon-protective effects in cultured neurons; however, its ability to block degeneration in vivo has been difficult to establish due to its poor cell permeability and serum instability. Here, we describe a strategy to increase cochlear NAD(+) levels in mice by administering nicotinamide riboside (NR), a recently described NAD(+) precursor. We find that administration of NR, even after noise exposure, prevents noise-induced hearing loss (NIHL) and spiral ganglia neurite degeneration. These effects are mediated by the NAD(+)-dependent mitochondrial sirtuin, SIRT3, since SIRT3-overexpressing mice are resistant to NIHL and SIRT3 deletion abrogates the protective effects of NR and expression of NAD(+) biosynthetic enzymes. These findings reveal that administration of NR activates a NAD(+)-SIRT3 pathway that reduces neurite degeneration caused by noise exposure.

• 出版日期2014-12-2