Increased nuclear NAD biosynthesis and SIRT1 activation prevent axonal degeneration - PubMed (original) (raw)

. 2004 Aug 13;305(5686):1010-3.

doi: 10.1126/science.1098014.

Affiliations

• PMID: 15310905
• DOI: 10.1126/science.1098014

Increased nuclear NAD biosynthesis and SIRT1 activation prevent axonal degeneration

Toshiyuki Araki et al. Science. 2004.

Abstract

Axonal degeneration is an active program of self-destruction that is observed in many physiological and pathological settings. In Wallerian degeneration slow (wlds) mice, Wallerian degeneration in response to axonal injury is delayed because of a mutation that results in overexpression of a chimeric protein (Wlds) composed of the ubiquitin assembly protein Ufd2a and the nicotinamide adenine dinucleotide (NAD) biosynthetic enzyme Nmnat1. We demonstrate that increased Nmnat activity is responsible for the axon-sparing activity of the Wlds protein. Furthermore, we demonstrate that SIRT1, a mammalian ortholog of Sir2, is the downstream effector of increased Nmnat activity that leads to axonal protection. These findings suggest that novel therapeutic strategies directed at increasing the supply of NAD and/or Sir2 activation may be effective for treatment of diseases characterized by axonopathy and neurodegeneration.

PubMed Disclaimer

Comment in

• Neuroscience. NAD to the rescue.
  Bedalov A, Simon JA. Bedalov A, et al. Science. 2004 Aug 13;305(5686):954-5. doi: 10.1126/science.1102497. Science. 2004. PMID: 15310883 No abstract available.

Similar articles

• Neuroscience. NAD to the rescue.
  Bedalov A, Simon JA. Bedalov A, et al. Science. 2004 Aug 13;305(5686):954-5. doi: 10.1126/science.1102497. Science. 2004. PMID: 15310883 No abstract available.
• A local mechanism mediates NAD-dependent protection of axon degeneration.
  Wang J, Zhai Q, Chen Y, Lin E, Gu W, McBurney MW, He Z. Wang J, et al. J Cell Biol. 2005 Aug 1;170(3):349-55. doi: 10.1083/jcb.200504028. Epub 2005 Jul 25. J Cell Biol. 2005. PMID: 16043516 Free PMC article.
• Nicotinamide mononucleotide adenylyltransferase expression in mitochondrial matrix delays Wallerian degeneration.
  Yahata N, Yuasa S, Araki T. Yahata N, et al. J Neurosci. 2009 May 13;29(19):6276-84. doi: 10.1523/JNEUROSCI.4304-08.2009. J Neurosci. 2009. PMID: 19439605 Free PMC article.
• Wallerian degeneration, wld(s), and nmnat.
  Coleman MP, Freeman MR. Coleman MP, et al. Annu Rev Neurosci. 2010;33:245-67. doi: 10.1146/annurev-neuro-060909-153248. Annu Rev Neurosci. 2010. PMID: 20345246 Free PMC article. Review.
• Tracking in the Wlds--the hunting of the SIRT and the luring of the Draper.
  Fainzilber M, Twiss JL. Fainzilber M, et al. Neuron. 2006 Jun 15;50(6):819-21. doi: 10.1016/j.neuron.2006.05.023. Neuron. 2006. PMID: 16772165 Review.

Cited by

• Comparison of red-shifted firefly luciferase Ppy RE9 and conventional Luc2 as bioluminescence imaging reporter genes for in vivo imaging of stem cells.
  Liang Y, Walczak P, Bulte JW. Liang Y, et al. J Biomed Opt. 2012 Jan;17(1):016004. doi: 10.1117/1.JBO.17.1.016004. J Biomed Opt. 2012. PMID: 22352654 Free PMC article.
• Effects of NAD+ in Caenorhabditis elegans Models of Neuronal Damage.
  Lee Y, Jeong H, Park KH, Kim KW. Lee Y, et al. Biomolecules. 2020 Jul 2;10(7):993. doi: 10.3390/biom10070993. Biomolecules. 2020. PMID: 32630651 Free PMC article. Review.
• Deletion of CD38 and supplementation of NAD+ attenuate axon degeneration in a mouse facial nerve axotomy model.
  Takaso Y, Noda M, Hattori T, Roboon J, Hatano M, Sugimoto H, Brenner C, Yamamoto Y, Okamoto H, Higashida H, Ito M, Yoshizaki T, Hori O. Takaso Y, et al. Sci Rep. 2020 Oct 20;10(1):17795. doi: 10.1038/s41598-020-73984-3. Sci Rep. 2020. PMID: 33082370 Free PMC article.
• Mitochondrial Dynamics Decrease Prior to Axon Degeneration Induced by Vincristine and are Partially Rescued by Overexpressed cytNmnat1.
  Berbusse GW, Woods LC, Vohra BP, Naylor K. Berbusse GW, et al. Front Cell Neurosci. 2016 Jul 19;10:179. doi: 10.3389/fncel.2016.00179. eCollection 2016. Front Cell Neurosci. 2016. PMID: 27486387 Free PMC article.
• Insights on attenuating autophagy cellular and molecular pathways versus methotrexate-induced toxicity via liposomal turmeric therapy.
  Kadry MO, Ammar NM, Hassan HA, Abdel Megeed RM. Kadry MO, et al. J Genet Eng Biotechnol. 2022 Oct 27;20(1):147. doi: 10.1186/s43141-022-00430-4. J Genet Eng Biotechnol. 2022. PMID: 36301384 Free PMC article.

Publication types

MeSH terms

Substances

LinkOut - more resources

• Full Text Sources

  • Atypon
  • Ovid Technologies, Inc.

• Other Literature Sources

  • H1 Connect
  • The Lens - Patent Citations Database

• Molecular Biology Databases

  • GlyGen glycoinformatics resource
  • Mouse Genome Informatics (MGI)