NAD+ supplementation normalizes key Alzheimer’s features and DNA damage responses in a new AD mouse model with introduced DNA repair deficiency

Proceedings of the National Academy of Sciences of the United States of America

Volumn 115, Issue 8, 2018, Pages E1876-E1885

  Hou, Yujun ^a   Lautrup, Sofie ^a,b   Cordonnier, Stephanie ^a   Wang, Yue ^a   Croteau, Deborah L ^a   Zavala, Eduardo ^a   Zhang, Yongqing ^a   Moritoh, Kanako ^a   O’Connell, Jennifer F ^a   Baptiste, Beverly A ^a   Stevnsner, Tinna V ^b   Mattson, Mark P ^a,c   Bohr, Vilhelm A ^a,d  

^a NATIONAL INSTITUTE ON AGING   (United States)

^b AARHUS UNIVERSITY   (Denmark)

^c JOHNS HOPKINS UNIVERSITY SCHOOL OF MEDICINE   (United States)

^d UNIVERSITY OF COPENHAGEN   (Denmark)

Author keywords

Aging; Alzheimer s disease; DNA repair; NAD supplementation; Nicotinamide riboside

Indexed keywords

AMYLOID BETA PROTEIN; NICOTINAMIDE ADENINE DINUCLEOTIDE; NICOTINAMIDE RIBOSIDE; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE; SIRTUIN 3; SIRTUIN 6; TAU PROTEIN; NICOTINAMIDE; NICOTINAMIDE-BETA-RIBOSIDE; SIRT3 PROTEIN, MOUSE; SIRT6 PROTEIN, MOUSE; SIRTUIN;

ALZHEIMER DISEASE; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTIINFLAMMATORY ACTIVITY; ANTIOXIDANT ACTIVITY; APOPTOSIS; ARTICLE; COGNITIVE DEFECT; CONTROLLED STUDY; DNA DAMAGE RESPONSE; DNA REPAIR; FEMALE; FIBROBLAST; HIPPOCAMPUS; HUMAN; HUMAN CELL; LONG TERM POTENTIATION; MALE; MOUSE; MOUSE MODEL; NERVE CELL PLASTICITY; NERVE DEGENERATION; NERVOUS SYSTEM INFLAMMATION; NONHUMAN; OXIDATIVE STRESS; PRIORITY JOURNAL; SYNAPTIC TRANSMISSION; WORKING MEMORY; ANALOGS AND DERIVATIVES; ANIMAL; DISEASE MODEL; DNA DAMAGE; DRUG EFFECT; GENE EXPRESSION REGULATION; GENETICS; METABOLISM; NERVOUS SYSTEM DEVELOPMENT; TRANSGENIC MOUSE;

ALZHEIMER DISEASE; ANIMALS; COGNITIVE DYSFUNCTION; DISEASE MODELS, ANIMAL; DNA DAMAGE; GENE EXPRESSION REGULATION; MALE; MICE; MICE, TRANSGENIC; NAD; NEUROGENESIS; NIACINAMIDE; SIRTUIN 3; SIRTUINS; TAU PROTEINS;

EID: 85042199670     PISSN: 00278424     EISSN: 10916490     Source Type: Journal    
DOI: 10.1073/pnas.1718819115     Document Type: Article

References (68)

1. Alzheimer’s A; Alzheimer’s Association (2016) 2016 Alzheimer’s disease facts and figures. Alzheimers Dement 12:459–509.
2. Hardy J, Selkoe DJ (2002) The amyloid hypothesis of Alzheimer’s disease: Progress and problems on the road to therapeutics. Science 297:353–356.
3. Selkoe DJ (2002) Deciphering the genesis and fate of amyloid beta-protein yields novel therapies for Alzheimer disease. J Clin Invest 110:1375–1381.
4. Hou Y, Song H, Croteau DL, Akbari M, Bohr VA (2017) Genome instability in Alzheimer disease. Mech Ageing Dev 161:83–94.
5. Wyss-Coray T (2006) Inflammation in Alzheimer disease: Driving force, bystander or beneficial response? Nat Med 12:1005–1015.
6. Kerr JS, et al. (2017) Mitophagy and Alzheimer’s disease: Cellular and molecular mechanisms. Trends Neurosci 40:151–166.
7. Bonkowski MS, Sinclair DA (2016) Slowing ageing by design: The rise of NAD+ and sirtuin-activating compounds. Nat Rev Mol Cell Biol 17:679–690.
8. Cantó C, Menzies KJ, Auwerx J (2015) NAD(+) metabolism and the control of energy homeostasis: A balancing act between mitochondria and the nucleus. Cell Metab 22: 31–53.
9. + in aging, metabolism, and neurodegeneration. Science 350: 1208–1213.
10. Cantó C, Sauve AA, Bai P (2013) Crosstalk between poly(ADP-ribose) polymerase and sirtuin enzymes. Mol Aspects Med 34:1168–1201.
11. Fang EF, et al. (2014) Defective mitophagy in XPA via PARP-1 hyperactivation and NAD(+)/SIRT1 reduction. Cell 157:882–896.
12. Fang EF, et al. (2016) NAD+ replenishment improves lifespan and healthspan in ataxia telangiectasia models via mitophagy and DNA repair. Cell Metab 24:566–581.
13. Long AN, et al. (2015) Effect of nicotinamide mononucleotide on brain mitochondrial respiratory deficits in an Alzheimer’s disease-relevant murine model. BMC Neurol 15:19.
14. Wang X, Hu X, Yang Y, Takata T, Sakurai T (2016) Nicotinamide mononucleotide protects against β-amyloid oligomer-induced cognitive impairment and neuronal death. Brain Res 1643:1–9.
15. Birkmayer JG, Vrecko C, Volc D, Birkmayer W (1993) Nicotinamide adenine dinucleotide (NADH)–A new therapeutic approach to Parkinson’s disease. Comparison of oral and parenteral application. Acta Neurol Scand Suppl 146:32–35.
16. Liu D, et al. (2013) Nicotinamide forestalls pathology and cognitive decline in Alzheimer mice: Evidence for improved neuronal bioenergetics and autophagy procession. Neurobiol Aging 34:1564–1580.
17. Scheibye-Knudsen M, et al. (2014) A high-fat diet and NAD(+) activate Sirt1 to rescue premature aging in cockayne syndrome. Cell Metab 20:840–855.
18. + repletion improves mitochondrial and stem cell function and enhances life span in mice. Science 352:1436–1443.
19. Jeppesen DK, Bohr VA, Stevnsner T (2011) DNA repair deficiency in neurodegeneration. Prog Neurobiol 94:166–200.
20. Obulesu M, Rao DM (2010) DNA damage and impairment of DNA repair in Alzheimer’s disease. Int J Neurosci 120:397–403.
21. Wang J, Markesbery WR, Lovell MA (2006) Increased oxidative damage in nuclear and mitochondrial DNA in mild cognitive impairment. J Neurochem 96:825–832.
22. Bradley-Whitman MA, et al. (2014) Nucleic acid oxidation: An early feature of Alzheimer’s disease. J Neurochem 128:294–304.
23. Lovell MA, Markesbery WR (2007) Oxidative DNA damage in mild cognitive impairment and late-stage Alzheimer’s disease. Nucleic Acids Res 35:7497–7504.
24. Chow HM, Herrup K (2015) Genomic integrity and the ageing brain. Nat Rev Neurosci 16:672–684.
25. Martire S, Mosca L, d’Erme M (2015) PARP-1 involvement in neurodegeneration: A focus on Alzheimer’s and Parkinson’s diseases. Mech Ageing Dev 146–148:53–64.
26. Martire S, et al. (2016) Bioenergetic impairment in animal and cellular models of Alzheimer’s disease: PARP-1 inhibition rescues metabolic dysfunctions. J Alzheimers Dis 54:307–324.
27. Sykora P, et al. (2013) Modulation of DNA base excision repair during neuronal differentiation. Neurobiol Aging 34:1717–1727.
28. Wei W, Englander EW (2008) DNA polymerase beta-catalyzed-PCNA independent long patch base excision repair synthesis: A mechanism for repair of oxidatively damaged DNA ends in post-mitotic brain. J Neurochem 107:734–744.
29. Weissman L, et al. (2007) Defective DNA base excision repair in brain from individuals with Alzheimer’s disease and amnestic mild cognitive impairment. Nucleic Acids Res 35:5545–5555.
30. Copani A, et al. (2006) DNA polymerase-beta is expressed early in neurons of Alzheimer’s disease brain and is loaded into DNA replication forks in neurons challenged with beta-amyloid. J Neurosci 26:10949–10957.
31. Patterson D, Cabelof DC (2012) Down syndrome as a model of DNA polymerase beta haploinsufficiency and accelerated aging. Mech Ageing Dev 133:133–137.
32. Raji NS, Rao KS (1998) Trisomy 21 and accelerated aging: DNA-repair parameters in peripheral lymphocytes of Down’s syndrome patients. Mech Ageing Dev 100:85–101.
33. Oddo S, et al. (2003) Triple-transgenic model of Alzheimer’s disease with plaques and tangles: Intracellular Abeta and synaptic dysfunction. Neuron 39:409–421.
34. Jankowsky JL, et al. (2004) Mutant presenilins specifically elevate the levels of the 42 residue beta-amyloid peptide in vivo: Evidence for augmentation of a 42-specific gamma secretase. Hum Mol Genet 13:159–170.
35. Sykora P, et al. (2015) DNA polymerase β deficiency leads to neurodegeneration and exacerbates Alzheimer disease phenotypes. Nucleic Acids Res 43:943–959.
36. Misiak M, et al. (2016) DNA polymerase beta decrement triggers death of olfactory bulb cells and impairs olfaction in a mouse model of Alzheimer’s disease. Aging Cell 16:162–172.
37. Trammell SA, et al. (2016) Nicotinamide riboside is uniquely and orally bioavailable in mice and humans. Nat Commun 7:12948.
38. Frederick DW, et al. (2016) Loss of NAD homeostasis leads to progressive and reversible degeneration of skeletal muscle. Cell Metab 24:269–282.
39. + levels. Rejuvenation Res 17:62–69.
40. Mazoteras Muñoz V, et al. (2010) Gait and balance impairments in Alzheimer disease patients. Alzheimer Dis Assoc Disord 24:79–84.
41. O’Brien RJ, et al. (2009) Neuropathologic studies of the Baltimore Longitudinal Study of Aging (BLSA). J Alzheimers Dis 18:665–675.
42. Kashiwaya Y, et al. (2013) A ketone ester diet exhibits anxiolytic and cognition-sparing properties, and lessens amyloid and tau pathologies in a mouse model of Alzheimer’s disease. Neurobiol Aging 34:1530–1539.
43. Kim SY, Volsky DJ (2005) PAGE: Parametric analysis of gene set enrichment. BMC Bioinformatics 6:144.
44. Ogata H, et al. (1999) KEGG: Kyoto encyclopedia of genes and genomes. Nucleic Acids Res 27:29–34.
45. Fabregat A, et al. (2016) The Reactome pathway Knowledgebase. Nucleic Acids Res 44:D481–D487.
46. Kandel ER (2001) The molecular biology of memory storage: A dialogue between genes and synapses. Science 294:1030–1038.
47. Lie DC, Song H, Colamarino SA, Ming GL, Gage FH (2004) Neurogenesis in the adult brain: New strategies for central nervous system diseases. Annu Rev Pharmacol Toxicol 44:399–421.
48. Subramanian S, et al. (2010) CCR6: A biomarker for Alzheimer’s-like disease in a triple transgenic mouse model. J Alzheimers Dis 22:619–629.
49. Spillantini MG, Goedert M (2013) Tau pathology and neurodegeneration. Lancet Neurol 12:609–622.
50. Buerger K, et al. (2002) Differential diagnosis of Alzheimer disease with cerebrospinal fluid levels of tau protein phosphorylated at threonine 231. Arch Neurol 59: 1267–1272.
51. +. Science 352: 1396–1397.
52. Ramamoorthy M, et al. (2012) Sporadic Alzheimer disease fibroblasts display an oxidative stress phenotype. Free Radic Biol Med 53:1371–1380.
53. Croteau DL, Bohr VA (1997) Repair of oxidative damage to nuclear and mitochondrial DNA in mammalian cells. J Biol Chem 272:25409–25412.
54. Herceg Z, Wang ZQ (2001) Functions of poly(ADP-ribose) polymerase (PARP) in DNA repair, genomic integrity and cell death. Mutat Res 477:97–110.
55. Cheng A, et al. (2016) Mitochondrial SIRT3 mediates adaptive responses of neurons to exercise and metabolic and excitatory challenges. Cell Metab 23:128–142.
56. + precursor nicotinamide riboside protects from noise-induced hearing loss. Cell Metab 20:1059–1068.
57. Gong B, et al. (2013) Nicotinamide riboside restores cognition through an upregulation of proliferator-activated receptor-γ coactivator 1α regulated β-secretase 1 degradation and mitochondrial gene expression in Alzheimer’s mouse models. Neurobiol Aging 34:1581–1588.
58. Ryu D, et al. (2016) NAD+ repletion improves muscle function in muscular dystrophy and counters global PARylation. Sci Transl Med 8:361ra139.
59. Kaluski S, et al. (2017) Neuroprotective functions for the histone deacetylase SIRT6. Cell Rep 18:3052–3062.
60. Serrano-Pozo A, et al. (2013) Differential relationships of reactive astrocytes and microglia to fibrillar amyloid deposits in Alzheimer disease. J Neuropathol Exp Neurol 72:462–471.
61. Lee HJ, Hong YS, Jun W, Yang SJ (2015) Nicotinamide riboside ameliorates hepatic metaflammation by modulating NLRP3 inflammasome in a rodent model of type 2 diabetes. J Med Food 18:1207–1213.
62. Trammell SA, et al. (2016) Nicotinamide riboside opposes type 2 diabetes and neu-ropathy in mice. Sci Rep 6:26933.
63. Love S, Barber R, Wilcock GK (1999) Increased poly(ADP-ribosyl)ation of nuclear proteins in Alzheimer’s disease. Brain 122:247–253.
64. Vorhees CV, Williams MT (2006) Morris water maze: Procedures for assessing spatial and related forms of learning and memory. Nat Protoc 1:848–858.
65. Leger M, et al. (2013) Object recognition test in mice. Nat Protoc 8:2531–2537.
66. Ghosal K, et al. (2009) Alzheimer’s disease-like pathological features in transgenic mice expressing the APP intracellular domain. Proc Natl Acad Sci USA 106: 18367–18372.
67. Curzon P, Rustay NR, Browman KE (2009) Cued and contextual fear conditioning for rodents. Methods of Behavior Analysis in Neuroscience, Frontiers in Neuroscience, ed Buccafusco JJ (CRC, Boca Raton, FL), 2nd Ed.
68. Zhang J, et al. (2011) The AAA+ ATPase thorase regulates AMPA receptor-dependent synaptic plasticity and behavior. Cell 145:284–299.