Nicotinamide improves motor deficits and upregulates PGC-1α and BDNF gene expression in a mouse model of Huntington's disease
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Huntington's disease (HD) is a fatal autosomal dominant neurodegenerative disorder caused by an expansion of the polyglutamine (polyQ) repeat in exon-1 in the Huntingtin gene (HTT). This results in misfolding and accumulation of the huntingtin (htt) protein, forming nuclear and cytoplasmic inclusions. HD is associated with dysregulation of gene expression as well as mitochondrial dysfunction. We hypothesized that by improving transcriptional regulation of genes necessary for energy metabolism, the HD motor phenotype would also improve. We therefore examined the protective effects of nicotinamide (NAM), a well-characterized water-soluble B vitamin that is an inhibitor of sirtuin1/class III NAD(+)-dependent histone deacetylase (HDAC). In this study, both mini-osmotic pumps and drinking water deliveries were tested at 250 mg NAM/kg/day, using the B6.HDR6/1 transgenic mouse model. Results were similar for both modes of delivery, and there was no evidence of toxicity. We found that NAM treatment increased mRNA levels of brain-derived neurotrophic factor (BDNF), and Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), the master regulator of mitochondrial biogenesis. Protein levels of BDNF were also significantly increased. In addition, NAM treatment increased PGC-1α activation in HD mice, pointing to a possible mode of action as a therapeutic. Critically, NAM treatment was able to improve motor deficits associated with the HD phenotype, tested as time courses of open field, rotarod, and balance beam activities. These improvements were substantial, despite the fact that NAM did not appear to reduce htt aggregation, or to prevent late-stage weight loss. Our study therefore concludes that NAM or similar drugs may be beneficial in clinical treatment of the motor dysfunctions of HD, while additional therapeutic approaches must be added to combat the aggregation phenotype and overall physiological decline.
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In neurodegenerative mouse models including AD, HD, and premature aging A-T, NAD+ augmentation increases BDNF expression and activity, leading to enhanced synaptic plasticity and function.
“In different neurodegenerative mouse models including AD, HD, and the premature aging disease A-T, NAD+ augmentation increases the expression and activity of BDNF, leading to enhanced synaptic plasticity and function (Fang et al., 2016a; Hathorn et al., 2011; Liu et al., 2013).”
From NAD+ in Brain Aging and Neurodegenerative Disorders (2019) · cites this paper as Hathorn et al., 2011
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Lagouge, M., Argmann, C., Gerhart-Hines, Z., Meziane, H., Lerin, C., Daussin, F., Messadeq, N., Milne, J., Lambert, P., Elliott, P., et al. (2006) · Cell · doi:10.1016/j.cell.2006.11.013 · Cited by 4,057 · see citing works
Transcriptional silencing and longevity protein Sir2 is an NAD-dependent histone deacetylase
Imai, S.-I., Armstrong, C. M., Kaeberlein, M., & Guarente, L. (2000) · Nature · doi:10.1038/35001622 · Cited by 3,510 · see citing works
Mangiarini, L., Sathasivam, K., Seller, M., Cozens, B., Harper, A., Hetherington, C., Lawton, M., Trottier, Y., Lehrach, H., Davies, S. W., et al. (1996) · Cell · doi:10.1016/s0092-8674(00)81369-0 · Cited by 3,073 · see citing works
Aggregation of Huntingtin in Neuronal Intranuclear Inclusions and Dystrophic Neurites in Brain
DiFiglia, M., Sapp, E., Chase, K. O., Davies, S. W., Bates, G. P., Vonsattel, J., & D, N. A. M. (1997) · Science · doi:10.1126/science.277.5334.1990 · Cited by 2,849 · see citing works
Davies, S. W., Turmaine, M., Cozens, B. A., DiFiglia, M., Sharp, A. H., Ross, C. A., Scherzinger, E., Wanker, E. E., Mangiarini, L., & Bates, G. P. (1997) · Cell · doi:10.1016/s0092-8674(00)80513-9 · Cited by 2,188 · see citing works
Dent, S., Denu, J. M., & Allis, C. D. (2001) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.70.1.81 · Cited by 1,844 · see citing works
Loss of Huntingtin-Mediated BDNF Gene Transcription in Huntington's Disease
Zuccato, C., Ciammola, A., Rigamonti, D., Leavitt, B. R., Goffredo, D., Conti, L., MacDonald, M. E., Friedlander, R. M., Silani, V., Hayden, M. R., et al. (2001) · Science · doi:10.1126/science.1059581 · Cited by 1,319 · see citing works
Histone deacetylase inhibitors arrest polyglutamine-dependent neurodegeneration in Drosophila
Steffan, J. S., Bodai, L., Pallos, J., Poelman, M., McCampbell, A., Apostol, B. L., Kazantsev, A., Schmidt, E., Zhu, Y.-Z., Greenwald, M., et al. (2001) · Nature · doi:10.1038/35099568 · Cited by 1,228 · see citing works
Defects in Adaptive Energy Metabolism with CNS-Linked Hyperactivity in PGC-1α Null Mice
Lin, J., Wu, P.-H., Tarr, P. T., Lindenberg, K. S., St-Pierre, J., Zhang, C.-Y., Mootha, V. K., Jäger, S., Vianna, C. R., Reznick, R. M., et al. (2004) · Cell · doi:10.1016/j.cell.2004.09.013 · Cited by 1,162 · see citing works
Handschin, C., & Spiegelman, B. M. (2006) · Endocrine Reviews · doi:10.1210/er.2006-0037 · Cited by 1,090 · see citing works
Trinucleotide repeat length instability and age of onset in Huntington's disease
Duyao, M., Ambrose, C., Myers, R., Novelletto, A., Persichetti, F., Frontali, M., Folstein, S., Ross, C., Franz, M., Abbott, M., et al. (1993) · Nature Genetics · doi:10.1038/ng0893-387 · Cited by 1,089 · see citing works
SIRT1 Functionally Interacts with the Metabolic Regulator and Transcriptional Coactivator PGC-1α
Nemoto, S., Fergusson, M. M., & Finkel, T. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m501485200 · Cited by 1,047 · see citing works
Cui, L., Jeong, H., Borovecki, F., Parkhurst, C. N., Tanese, N., & Krainc, D. (2006) · Cell · doi:10.1016/j.cell.2006.09.015 · Cited by 1,012 · see citing works
Bitterman, K. J., Anderson, R. M., Cohen, H. Y., Latorre-Esteves, M., & Sinclair, D. A. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m205670200 · Cited by 1,002 · see citing works
Leone, T. C., Lehman, J. J., Finck, B. N., Schaeffer, P. J., Wende, A. R., Boudina, S., Courtois, M., Wozniak, D. F., Sambandam, N., Bernal-Mizrachi, C., et al. (2005) · PLoS Biology · doi:10.1371/journal.pbio.0030101 · Cited by 951 · see citing works
Brain-derived neurotrophic factor in neurodegenerative diseases
Zuccato, C., & Cattaneo, E. (2009) · Nature Reviews Neurology · doi:10.1038/nrneurol.2009.54 · Cited by 947 · see citing works
Hockly, E., Richon, V. M., Woodman, B., Smith, D. L., Zhou, X., Rosa, E., Sathasivam, K., Ghazi‐Noori, S., Mahal, A., Lowden, P. A. S., et al. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0437870100 · Cited by 847 · see citing works
Huntingtin interacts with REST/NRSF to modulate the transcription of NRSE-controlled neuronal genes
Zuccato, C., Tartari, M., Crotti, A., Goffredo, D., Valenza, M., Conti, L., Cataudella, T., Leavitt, B. R., Hayden, M. R., Timmusk, T., et al. (2003) · Nature Genetics · doi:10.1038/ng1219 · Cited by 814 · see citing works
Decreased expression of striatal signaling genes in a mouse model of Huntington's disease
Luthi‐Carter, R. (2000) · Human Molecular Genetics · doi:10.1093/hmg/9.9.1259 · Cited by 723 · see citing works
Ferrante, R. J., Kubilus, J. K., Lee, J.-H., Ryu, H., Beesen, A. A., Zucker, B., Smith, K., Kowall, N. W., Ratan, R. R., Luthi‐Carter, R., et al. (2003) · Journal of Neuroscience · doi:10.1523/jneurosci.23-28-09418.2003 · Cited by 694 · see citing works
Weydt, P., Pineda, V. V., Torrence, A. E., Libby, R. T., Satterfield, T. F., Lazarowski, E. R., Gilbert, M. L., Morton, G. J., Bammler, T. K., Strand, A. D., et al. (2006) · Cell Metabolism · doi:10.1016/j.cmet.2006.10.004 · Cited by 562 · see citing works
Motor Coordination and Balance in Rodents
Carter, R. J., Morton, J. P., & Dunnett, S. B. (2001) · Current Protocols in Neuroscience · doi:10.1002/0471142301.ns0812s15 · Cited by 479 · see citing works
Sirtuins as potential targets for metabolic syndrome
Guarente, L. (2006) · Nature · doi:10.1038/nature05486 · Cited by 468 · see citing works
Nonapoptotic neurodegeneration in a transgenic mouse model of Huntington's disease
Turmaine, M., Raza, A., Mahal, A., Mangiarini, L., Bates, G. P., & Davies, S. W. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.110078997 · Cited by 430 · see citing works
N-Terminal Mutant Huntingtin Associates with Mitochondria and Impairs Mitochondrial Trafficking
Orr, A. L., Li, S., Wang, C.-E., Li, H., Wang, J., Rong, J., Xu, X., Mastroberardino, P. G., Greenamyre, J. T., & Li, X. (2008) · Journal of Neuroscience · doi:10.1523/jneurosci.0106-08.2008 · Cited by 429 · see citing works
Safety of high-dose nicotinamide: a review
Knip, M., Douek, I. F., Moore, W. P. T., Gillmor, H. A., McLean, A. E. M., Bingley, P. J., & Gale, E. A. M. (2000) · Diabetologia · doi:10.1007/s001250051536 · Cited by 423 · see citing works
Green, K. N., Steffan, J. S., Martinez-Coria, H., Sun, X., Schreiber, S. S., Thompson, L. M., & LaFerla, F. M. (2008) · The Journal of Neuroscience · doi:10.1523/jneurosci.3203-08.2008 · Cited by 404 · see citing works
Transcriptional dysregulation in Huntington’s disease
Cha, J.-H. J. (2000) · Trends in Neurosciences · doi:10.1016/s0166-2236(00)01609-x · Cited by 399 · see citing works
Polyglutamine diseases: emerging concepts in pathogenesis and therapy
Shao, J., & Diamond, M. I. (2007) · Human Molecular Genetics · doi:10.1093/hmg/ddm213 · Cited by 284 · see citing works
Rine, J., Strathern, J. N., Hicks, J. B., & Herskowitz, I. (1979) · Genetics · doi:10.1093/genetics/93.4.877 · Cited by 268 · see citing works
Pallos, J., Bodai, L., Lukácsovich, T., Purcell, J. M., Steffan, J. S., Thompson, L. M., & Marsh, J. (2008) · Human Molecular Genetics · doi:10.1093/hmg/ddn273 · Cited by 265 · see citing works
Southwell, A. L., Ko, J., & Patterson, P. H. (2009) · Journal of Neuroscience · doi:10.1523/jneurosci.4286-09.2009 · Cited by 233 · see citing works
Histone deacetylase inhibitors as therapeutics for polyglutamine disorders
Butler, R. K., & Bates, G. P. (2006) · Nature reviews. Neuroscience · doi:10.1038/nrn1989 · Cited by 212 · see citing works
Biological and Potential Therapeutic Roles of Sirtuin Deacetylases
Taylor, D. M., Maxwell, M. M., Luthi‐Carter, R., & Kazantsev, A. G. (2008) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-008-8357-y · Cited by 147 · see citing works
Szapacs, M. E., Mathews, T. A., Tessarollo, L., Lyons, W. E., Mamounas, L. A., & Andrews, A. M. (2004) · Journal of Neuroscience Methods · doi:10.1016/j.jneumeth.2004.03.026 · Cited by 147 · see citing works
Suppression of Huntington's disease pathology in Drosophila by human single-chain Fv antibodies
Wolfgang, W. J., Miller, T. W., Webster, J. M., Huston, J. S., Thompson, L. M., Marsh, J., & Messer, A. C. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0505321102 · Cited by 142 · see citing works
Self-citationSelective deficits in the expression of striatal‐enriched mRNAs in Huntington's disease
Desplats, P., Kass, K. E., Gilmartin, T., Stanwood, G. D., Woodward, E. L., Head, S. R., Sutcliffe, J. G., & Thomas, E. A. (2006) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2005.03588.x · Cited by 133 · see citing works
Nonomura, T., Tsuchida, A., Ono‐Kishino, M., Nakagawa, T., Taiji, M., & Noguchia, H. (2001) · Journal of Diabetes Research · doi:10.1155/edr.2001.201 · Cited by 131 · see citing works
PGC-1α, a New Therapeutic Target in Huntington's Disease?
McGill, J. K., & Beal, M. F. (2006) · Cell · doi:10.1016/j.cell.2006.10.023 · Cited by 131 · see citing works
Weiss, A., Klein, C., Woodman, B., Sathasivam, K., Bibel, M., Régulier, E., Bates, G. P., & Paganetti, P. (2007) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2007.05032.x · Cited by 113 · see citing works
Modulation of SIRT1 expression in different neurodegenerative models and human pathologies
Pallàs, M., Pizarro, J. G., Cuesta, J., Crespo‐Biel, N., Alvira, D., Tajes, M., Yeste‐Velasco, M., Folch, J., Canudas, A. M., Sureda, F. X., et al. (2008) · Neuroscience · doi:10.1016/j.neuroscience.2008.04.065 · Cited by 112 · see citing works
Ghosh, S., & Feany, M. Β. (2004) · Human Molecular Genetics · doi:10.1093/hmg/ddh214 · Cited by 106 · see citing works
Jia, H., Li, X., Gao, H., Feng, Z., Li, X., Zhao, L., Jia, X., Zhang, H., & Liu, J. (2008) · Journal of Neuroscience Research · doi:10.1002/jnr.21650 · Cited by 98 · see citing works
Early Alterations in Gene Expression and Cell Morphology in a Mouse Model of Huntington's Disease
Iannicola, C., Moreno, S., Oliverio, S., Nardacci, R., Ciofi-Luzzatto, A., & Piacentini, M. (2000) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2000.0750830.x · Cited by 74 · see citing works
Snyder‐Keller, A., McLear, J. A., Hathorn, T., & Messer, A. C. (2010) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0b013e3181f530ec · Cited by 73 · see citing works
Self-citationEarly exploratory behavior abnormalities in R6/1 Huntington's disease transgenic mice
Bolivar, V. J., MANLEY, K. M., & Messer, A. C. (2004) · Brain Research · doi:10.1016/j.brainres.2004.01.021 · Cited by 63 · see citing works
Self-citationNicotinamide treatment in the prevention of insulin‐dependent diabetes mellitus
Mandrup-Poulsen, T. R., Reimers, J. I., Andersen, H. U., Pociot, F., Karlsen, A. E., Christensen, U. B., & Nerup, J. (1993) · Diabetes/Metabolism Reviews · doi:10.1002/dmr.5610090410 · Cited by 46 · see citing works
Dillin, A. G., & Kelly, J. W. (2007) · Science · doi:10.1126/science.1146585 · Cited by 40 · see citing works
McLear, J. A., Lebrecht, D., Messer, A. C., & Wolfgang, W. J. (2008) · The FASEB Journal · doi:10.1096/fj.07-099689 · Cited by 39 · see citing works
Self-citationTranscription meets metabolism in neurodegeneration
Ross, C. A., & Thompson, L. M. (2006) · Nature Medicine · doi:10.1038/nm1106-1239 · Cited by 30 · see citing works
Bortvedt, S. F., McLear, J. A., Messer, A. C., Ahern‐Rindell, A. J., & Wolfgang, W. J. (2010) · Neurobiology of Disease · doi:10.1016/j.nbd.2010.04.007 · Cited by 24 · see citing works
Self-citationPabello, N. G., Tracy, S. J., Snyder‐Keller, A., & Keller, R. W. (2005) · Brain Research · doi:10.1016/j.brainres.2004.12.047 · Cited by 19 · see citing works
Self-citationEnhancement of brain choline levels by nicotinamide: mechanism of action
Erb, C., & Klein, J. (1998) · Neuroscience Letters · doi:10.1016/s0304-3940(98)00418-2 · Cited by 16 · see citing works
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Xie, N., Zhang, L., Gao, W. Q., Huang, C., Huber, P., Zhou, X., Li, C. L., Shen, G., & Zou, B. (2020) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-020-00311-7 · Cited by 1,076 · see citing works
NAD+ in Brain Aging and Neurodegenerative Disorders
Lautrup, S., Sinclair, D. A., Mattson, M. P., & Fang, E. F. (2019) · Cell Metabolism · doi:10.1016/j.cmet.2019.09.001 · Cited by 790 · see citing works
Luen Tang, B. (2016) · Molecules and Cells · doi:10.14348/molcells.2016.2318 · Cited by 740 · see citing works
SIRT1 in Neurodevelopment and Brain Senescence
Herskovits, A. Z., & Guarente, L. (2014) · Neuron · doi:10.1016/j.neuron.2014.01.028 · Cited by 493 · see citing works
The emerging field of epigenetics in neurodegeneration and neuroprotection
Hwang, J.-Y., Aromolaran, K. A., & Zukin, R. S. (2017) · Nature reviews. Neuroscience · doi:10.1038/nrn.2017.46 · Cited by 343 · see citing works
Niacin in the Central Nervous System: An Update of Biological Aspects and Clinical Applications
Gasperi, V., Sibilano, M., Savini, I., & Catani, M. V. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20040974 · Cited by 282 · see citing works
Liu, D., Pitta, M., Jiang, H., Lee, J.-H., Zhang, G., Chen, X., Kawamoto, E. M., & Mattson, M. P. (2013) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2012.11.020 · Cited by 238 · see citing works
Epigenetic targeting of histone deacetylase: Therapeutic potential in Parkinson's disease?
Harrison, I. F., & Dexter, D. T. (2013) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2013.05.010 · Cited by 227 · see citing works
The Influence of Nicotinamide on Health and Disease in the Central Nervous System
Fricker, R. A., Green, E. L., Jenkins, S. I., & Griffin, S. M. (2018) · International Journal of Tryptophan Research · doi:10.1177/1178646918776658 · Cited by 200 · see citing works
SIRT1 and SIRT2 Activity Control in Neurodegenerative Diseases
Manjula, R., Anuja, K., & Alcain, F. J. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2020.585821 · Cited by 193 · see citing works
New Avenues for the Treatment of Huntington’s Disease
Kim, A. M., Lalonde, K. M., Truesdell, A., Welter, P. G., Brocardo, P. S., Rosenstock, T. R., & Gil‐Mohapel, J. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22168363 · Cited by 198 · see citing works
Possible Adverse Effects of High-Dose Nicotinamide: Mechanisms and Safety Assessment
Hwang, E., & Song, S. (2020) · Biomolecules · doi:10.3390/biom10050687 · Cited by 144 · see citing works
Role of oxidative DNA damage in mitochondrial dysfunction and Huntington’s disease pathogenesis
Ayala‐Peña, S. (2013) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2013.04.017 · Cited by 142 · see citing works
Naia, L., Rosenstock, T. R., Oliveira, A. M., Oliveira-Sousa, S. I., Caldeira, G. L., Carmo, C., Laço, M., Hayden, M. R., Oliveira, C. R., & Rego, A. C. (2016) · Molecular Neurobiology · doi:10.1007/s12035-016-0048-3 · Cited by 135 · see citing works
Bobrowska, A., Donmez, G., Weiss, A., Guarente, L., & Bates, G. (2012) · PLoS ONE · doi:10.1371/journal.pone.0034805 · Cited by 140 · see citing works
Xiang, Z., Valenza, M., Cui, L., Leoni, V., Jeong, H.-K., Brilli, E., Zhang, J., Peng, Q., Duan, W., Reeves, S. A., et al. (2011) · Journal of Neuroscience · doi:10.1523/jneurosci.1291-11.2011 · Cited by 132 · see citing works
The promise and perils of HDAC inhibitors in neurodegeneration
Didonna, A., & Opal, P. (2014) · Annals of Clinical and Translational Neurology · doi:10.1002/acn3.147 · Cited by 120 · see citing works
Lim, M. A., Selak, M. A., Xiang, Z., Krainc, D., Neve, R. L., Kraemer, B. C., Watts, J. L., & Kalb, R. G. (2012) · Journal of Neuroscience · doi:10.1523/jneurosci.6554-10.2012 · Cited by 99 · see citing works
PGC-1α sparks the fire of neuroprotection against neurodegenerative disorders
Lv, J., Jiang, S., Yang, Z. P., Hu, W., Wang, Z., Li, T. X., & Yang, Y. (2018) · Ageing Research Reviews · doi:10.1016/j.arr.2018.03.004 · Cited by 101 · see citing works
PPARgamma rescue of the mitochondrial dysfunction in Huntington's disease
Chiang, M., Chern, Y., & Huang, R. (2011) · Neurobiology of Disease · doi:10.1016/j.nbd.2011.08.016 · Cited by 99 · see citing works
D-β-Hydroxybutyrate Is Protective in Mouse Models of Huntington's Disease
Lim, S., Chesser, A. S., Grima, J. C., Rappold, P. M., Blum, D. L., Przedborski, S., & Tieu, K. (2011) · PLoS ONE · doi:10.1371/journal.pone.0024620 · Cited by 94 · see citing works
Optimizing intracellular antibodies (intrabodies/nanobodies) to treat neurodegenerative disorders
Messer, A. C., & Butler, D. C. (2019) · Neurobiology of Disease · doi:10.1016/j.nbd.2019.104619 · Cited by 91 · see citing works
Self-citationZuccato, C., & Cattaneo, E. F. (2014) · Handbook of experimental pharmacology · doi:10.1007/978-3-642-45106-5_14 · Cited by 92 · see citing works
NAMPT as a Therapeutic Target against Stroke
Wang, P., & Miao, C. (2015) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2015.08.012 · Cited by 86 · see citing works
Kumar, A., Vaish, M., & Ratan, R. R. (2014) · Drug Discovery Today · doi:10.1016/j.drudis.2014.03.016 · Cited by 82 · see citing works
Bouchecareilh, M., Hutt, D. M., Szajner, P., Flotte, T. R., & Balch, W. E. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.404707 · Cited by 83 · see citing works
Role of BDNF in Central Motor Structures and Motor Diseases
He, Y., Zhang, X., Yung, W., Zhu, J., & Wang, J. (2013) · Molecular Neurobiology · doi:10.1007/s12035-013-8466-y · Cited by 81 · see citing works
Ehrnhoefer, D. E., Wong, B. K. Y., & Hayden, M. R. (2011) · Nature Reviews Drug Discovery · doi:10.1038/nrd3556 · Cited by 78 · see citing works
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Song, S. B., Park, J., Chung, G. J., Lee, I. H., & Hwang, E. S. (2019) · Metabolomics · doi:10.1007/s11306-019-1604-4 · Cited by 72 · see citing works
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Huang, Y., Wang, S., Zhou, J., Liu, Y., Du, C., Yang, K., Bi, X., Liu, M., Han, W., Wang, K., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-18519-0 · Cited by 65 · see citing works
Butler, D. C., McLear, J. A., & Messer, A. C. (2011) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2011.11.004 · Cited by 62 · see citing works
Self-citationHarrison, I. F., Powell, N. M., & Dexter, D. T. (2018) · Journal of Neurochemistry · doi:10.1111/jnc.14599 · Cited by 59 · see citing works
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Lloret, A., & Beal, M. F. (2019) · Neurochemical Research · doi:10.1007/s11064-019-02809-1 · Cited by 52 · see citing works
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McCullough, S., Xu, X.-J., Dent, S., Bekiranov, S., Roeder, R., & Grant, P. (2012) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.1218331110 · Cited by 48 · see citing works
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Reynolds, R. H., Petersen, M. H., Willert, C. W., Heinrich, M., Nymann, N., Dall, M., Treebak, J. T., Björkqvist, M., Silahtaroglu, A., Hasholt, L., et al. (2017) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2017.12.009 · Cited by 43 · see citing works
Poly (ADP-ribose) polymerase 1 and neurodegenerative diseases: past, present, and future
Hu, M.-L., Pan, Y.-R., Yong, Y.-Y., Liu, Y., Yu, L., Qin, D.-L., Qiao, G., Law, B. Y.-K., Wu, J.-M., Zhou, X.-G., et al. (2023) · Ageing Research Reviews · doi:10.1016/j.arr.2023.102078 · Cited by 44 · see citing works
Epigenetics in Nucleotide Repeat Expansion Disorders
He, F., & Todd, P. K. (2011) · Seminars in Neurology · doi:10.1055/s-0031-1299786 · Cited by 42 · see citing works
Prospects for neuroprotective therapies in prodromal Huntington's disease
Chandra, A., Johri, A., & Beal, M. F. (2014) · Movement Disorders · doi:10.1002/mds.25835 · Cited by 41 · see citing works
Metabolism in HD: Still a relevant mechanism?
Duan, W., Jiang, M., & Jin, J. (2014) · Movement Disorders · doi:10.1002/mds.25992 · Cited by 41 · see citing works
The dysfunction of hepatic transcriptional factors in mice with Huntington's Disease
Chiang, M., Chern, Y., & Juo, C. (2011) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2011.05.006 · Cited by 41 · see citing works
Chen, C., Weng, Y., Chen, W.-L., Lin, T., Chao, C., Lin, C., Chen, I., Lee, L., Lin, H.-Y., Wu, Y., et al. (2014) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2014.03.023 · Cited by 41 · see citing works
Williams, A. C., Hill, L. J., & Ramsden, D. B. (2012) · Current Gerontology and Geriatrics Research · doi:10.1155/2012/302875 · Cited by 41 · see citing works
Rehman, I. U., Khan, A., Ahmad, R., Choe, K., Park, H. Y., Lee, H. J., Atiq, A., Park, J., Hahm, J. R., & Kim, M. O. (2022) · Biomedicines · doi:10.3390/biomedicines10112929 · Cited by 40 · see citing works
Lucas, E. K., Reid, C. S., McMeekin, L. J., Dougherty, S., Floyd, C. L., & Cowell, R. M. (2015) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2014.00441 · Cited by 40 · see citing works
Reiner, A., Lafferty, D., Wang, H. B., Mar, N. D., & Deng, Y. P. (2012) · Neurobiology of Disease · doi:10.1016/j.nbd.2012.03.025 · Cited by 39 · see citing works
Mouse Models of Polyglutamine Diseases in Therapeutic Approaches: Review and Data Table. Part II
Switonski, P. M., Szlachcic, W. J., Gabka, A., Krzyżosiak, W. J., & Figiel, M. (2012) · Molecular Neurobiology · doi:10.1007/s12035-012-8316-3 · Cited by 38 · see citing works
Xiang, C., Zhang, S., Dong, X., Ma, S., & Cong, S. (2018) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2018.00153 · Cited by 38 · see citing works
Intrabodies as Neuroprotective Therapeutics
Messer, A. C., & Joshi, S. N. (2013) · Neurotherapeutics · doi:10.1007/s13311-013-0193-6 · Cited by 34 · see citing works
Self-citationTherapeutic Strategies in Huntington’s Disease: From Genetic Defect to Gene Therapy
Jurcău, A., & Jurcău, M. C. (2022) · Biomedicines · doi:10.3390/biomedicines10081895 · Cited by 36 · see citing works
Wu, Y., Wang, Y., Yin, D., Wu, W., Sun, X., Zhang, Y., Guo, X., Chen, J., & Yuan, J. (2019) · Food & Function · doi:10.1039/c9fo00904c · Cited by 38 · see citing works
Wu, Y., Wang, Y., Yin, D., Mahmood, T., & Yuan, J. (2020) · BMC Genomics · doi:10.1186/s12864-020-06827-0 · Cited by 33 · see citing works
Mitophagy impairment in neurodegenerative diseases: Pathogenesis and therapeutic interventions
Mani, S., Swargiary, G., & Chadha, R. (2021) · Mitochondrion · doi:10.1016/j.mito.2021.01.001 · Cited by 32 · see citing works
NAD + Precursors in Human Health and Disease: Current Status and Future Prospects
Yaku, K., & Nakagawa, T. (2023) · Antioxidants and Redox Signaling · doi:10.1089/ars.2023.0354 · Cited by 31 · see citing works
Therapeutic approaches targeting aging and cellular senescence in Huntington's disease
Bhat, A. A., Moglad, E. H. O., Afzal, M., Thapa, R., Almalki, W. H., Kazmi, I. A., Alzarea, S. I., Ali, H., Pant, K., Singh, T. G., et al. (2024) · CNS Neuroscience & Therapeutics · doi:10.1111/cns.70053 · Cited by 32 · see citing works
Ieraci, A., & Herrera, D. G. (2018) · The Cerebellum · doi:10.1007/s12311-017-0916-z · Cited by 31 · see citing works
Wang, X., Mao, G.-H., Li, Q., Tang, J., Zhang, H., Wang, K.-L., Wang, L., Ni, H., Sheng, R., & Qin, Z. (2023) · Frontiers in Pharmacology · doi:10.3389/fphar.2023.1096533 · Cited by 31 · see citing works
Song, S. B., Park, J., Jang, S. Y., & Hwang, E. S. (2021) · Cells · doi:10.3390/cells10030612 · Cited by 30 · see citing works
Critical Role of Astrocyte NAD + Glycohydrolase in Myelin Injury and Regeneration
Langley, M. R., Choi, C., Peclat, T., Guo, Y., Simon, W. L., Yoon, H., Kleppe, L. S., Lucchinetti, C. F., Chini, C. C. S., Chini, E. N., et al. (2021) · Journal of Neuroscience · doi:10.1523/jneurosci.2264-20.2021 · Cited by 30 · see citing works
NAD+ Metabolism and Diseases with Motor Dysfunction
Lundt, S., & Ding, S. (2021) · Genes · doi:10.3390/genes12111776 · Cited by 27 · see citing works
Sadan, O., Melamed, E., & Offen, D. (2012) · PLoS Currents · doi:10.1371/4f7f6dc013d4e · Cited by 28 · see citing works
Nicotinamide Administration Improves Remyelination after Stroke
Wang, C., Zhang, Y., Ding, J., Zhao, Z., Qian, C., Luan, Y., & Teng, G. (2017) · Neural Plasticity · doi:10.1155/2017/7019803 · Cited by 27 · see citing works
Vibrational spectroscopic, molecular docking and quantum chemical studies on 6-aminonicotinamide
Asath, R. M., Premkumar, S., Mathavan, T., & Benial, A. M. F. (2016) · Journal of Molecular Structure · doi:10.1016/j.molstruc.2016.12.058 · Cited by 27 · see citing works
Mitochondrial targeted antioxidants as potential therapy for huntington’s disease
Upadhayay, S., & Kumar, P. (2024) · Pharmacological Reports · doi:10.1007/s43440-024-00619-z · Cited by 29 · see citing works
Gomes, P., Leal, H., Mendes, A. F., Reis, F., & Cavadas, C. (2019) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2019.09.003 · Cited by 27 · see citing works
Progresses in both basic research and clinical trials of NAD+ in Parkinson’s disease
Maria Jose Perez, J., Baden, P., & Deleidi, M. (2021) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2021.111499 · Cited by 25 · see citing works
Gonzalez, L., & Bezzi, P. (2025) · Journal of Neurochemistry · doi:10.1111/jnc.70092 · Cited by 24 · see citing works
Sirtuins as Modifiers of Huntington's Disease (HD) Pathology
Neo, S. H., & Tang, B. L. (2017) · Progress in molecular biology and translational science · doi:10.1016/bs.pmbts.2017.11.013 · Cited by 24 · see citing works
Firdaus, Z., & Li, X. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms252111658 · Cited by 23 · see citing works
Rowlands, B. D., Lau, C. L., Ryall, J. G., Thomas, D. S., Klugmann, M., Beart, P. M., & Rae, C. D. (2015) · Journal of Neuroscience Research · doi:10.1002/jnr.23570 · Cited by 23 · see citing works
Nicotinamide promotes neuronal differentiation of mouse embryonic stem cells in vitro
Griffin, S. M., Pickard, M. R., Orme, R. P., Hawkins, C., & Fricker, R. A. (2013) · Neuroreport · doi:10.1097/wnr.0000000000000071 · Cited by 23 · see citing works
Chen, C., Chen, W., Hung, C.-T., Lin, T., Lee, M.-C., Chen, I., Lin, C., Chao, C., Wu, Y., Chang, K., et al. (2019) · Aging · doi:10.18632/aging.101804 · Cited by 23 · see citing works
Differential Effect of HDAC3 on Cytoplasmic and Nuclear Huntingtin Aggregates
Mano, T., Suzuki, T., Tsuji, S., & Iwata, A. (2014) · PLoS ONE · doi:10.1371/journal.pone.0111277 · Cited by 22 · see citing works
Bioenergetics in fibroblasts of patients with Huntington disease are associated with age at onset
Gardiner, S. L., Milanese, C., Boogaard, M. W., Buijsen, R. A. M., Hogenboom, M., Roos, R. A. C., Mastroberardino, P. G., van Roon‐Mom, W., & Aziz, N. A. (2018) · Neurology Genetics · doi:10.1212/nxg.0000000000000275 · Cited by 20 · see citing works
Wang, L., Peng, T., Deng, J., Gao, W., Wang, H., Luo, O. J., Huang, L., & Chen, G. (2024) · Biochemical Pharmacology · doi:10.1016/j.bcp.2024.116272 · Cited by 19 · see citing works
Virtual Screening in the Identification of Sirtuins’ Activity Modulators
Abbotto, E., Scarano, N., Piacente, F., Millo, E., Cichero, E., & Bruzzone, S. (2022) · Molecules · doi:10.3390/molecules27175641 · Cited by 18 · see citing works
Engineered Extracellular Vesicles/Exosomes as a New Tool against Neurodegenerative Diseases
Ferrantelli, F., Chiozzini, C., Leone, P., Manfredi, F., & Federico, M. (2020) · Pharmaceutics · doi:10.3390/pharmaceutics12060529 · Cited by 17 · see citing works
Sustainable Design of New Ionic Forms of Vitamin B3 and Their Utilization as Plant Protection Agents
Stachowiak, W., Kaczmarek, D. K., Rzemieniecki, T., & Niemczak, M. (2022) · Journal of Agricultural and Food Chemistry · doi:10.1021/acs.jafc.2c01807 · Cited by 16 · see citing works
Kreiner, G., Soenmez, A., Liss, B., & Parlato, R. (2019) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2019.00106 · Cited by 15 · see citing works
Neurodegenerative diseases: Epigenetic regulatory mechanisms and therapeutic potential
Men, J., Wang, X., Zhou, Y., Huang, Y., Zheng, Y., Wang, Y., Yang, S., Chen, N., Yan, N., & Duan, X. (2025) · Cellular Signalling · doi:10.1016/j.cellsig.2025.111715 · Cited by 13 · see citing works
Characteristics, Pathophysiology and Clinical Management of Weight Loss in Huntington’s Disease
Aziz, N. A., & Roos, R. A. C. (2013) · Neurodegenerative Disease Management · doi:10.2217/nmt.13.22 · Cited by 13 · see citing works
Rollnik, J. D. (2015) · Der Nervenarzt · doi:10.1007/s00115-015-4306-9 · Cited by 13 · see citing works
Risks and rewards of targeting NAD+ homeostasis in the brain
Li, C., & Wu, L. E. (2021) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2021.111545 · Cited by 13 · see citing works
Polyglutamine disorders: Pathogenesis and potential drug interventions
Tandon, S., Aggarwal, P., & Sarkar, S. (2024) · Life Sciences · doi:10.1016/j.lfs.2024.122562 · Cited by 12 · see citing works
Potential therapeutic targets in polyglutamine-mediated diseases
Katsuno, M., Watanabe, H., Yamamoto, M., & Sobue, G. (2014) · Expert Review of Neurotherapeutics · doi:10.1586/14737175.2014.956727 · Cited by 12 · see citing works
Haar, C. V. (2013) · Clinical Pharmacology & Biopharmaceutics · doi:10.4172/2167-065x.s1-005 · Cited by 12 · see citing works
Salamon, A., Maszlag-Török, R., Veres, G., Boros, F. A., Vágvölgyi-Sümegi, E., Somogyi, A., Vécsei, L., Klivènyi, P., & Zádori, D. (2020) · Neurochemical Research · doi:10.1007/s11064-020-03069-0 · Cited by 11 · see citing works
Zeidler, J. D., Chini, C. C. S., Kanamori, K. S., Kashyap, S., Espíndola‐Netto, J. M., Thompson, K. D., Warner, G. M., Cabral, F. S., Peclat, T., Gomez, L. S., et al. (2022) · iScience · doi:10.1016/j.isci.2022.105431 · Cited by 10 · see citing works
Azman, K. F., & Zakaria, R. (2025) · Current Neuropharmacology · doi:10.2174/1570159x22666240530105516 · Cited by 10 · see citing works
Zhang, C., Shao, Q., Zhang, Y., Liu, W., Kang, J., Jin, Z., Huang, N., & Ning, B. (2024) · CNS Neuroscience & Therapeutics · doi:10.1111/cns.14826 · Cited by 11 · see citing works
Meng, Y., Song, C., Ren, Z., Li, X., Yang, X., Ai, N., Yang, Y., Wang, D., Zhan, M., Wang, J., et al. (2021) · Cell Death and Disease · doi:10.1038/s41419-021-04395-z · Cited by 9 · see citing works
Autophagy–NAD+ axis: emerging insights into neuronal homeostasis and neurodegenerative diseases
Koçak, G., Dimas, M. M., Silva, L., Silva-Amaral, D., Sun, C., Cruddas, S., Barrett, T. G., Martins‐de‐Souza, D., Cunha‐Neto, E., Brocardo, P. S., et al. (2025) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2025.1695486 · Cited by 8 · see citing works
Dietary NMN supplementation enhances motor and NMJ function in ALS
Lundt, S., Zhang, N., Polo‐Parada, L., Wang, X., & Ding, S. (2024) · Experimental Neurology · doi:10.1016/j.expneurol.2024.114698 · Cited by 8 · see citing works
Micheva‐Viteva, S., Ross, B. N., Gao, J., Adikari, S., Zhang, P., Mourant, J. R., Wu, T. H., Werner, J. H., Torres, A. G., & Hong‐Geller, E. (2018) · Infection and Immunity · doi:10.1128/iai.00592-18 · Cited by 8 · see citing works
CRISPR-Cas9 mediated genome editing of Huntington’s disease neurospheres
Han, J. Y., Seo, J., Choi, Y., Im, W., Ban, J., & Sung, J. (2022) · Molecular Biology Reports · doi:10.1007/s11033-022-08175-6 · Cited by 8 · see citing works
Novel Therapeutic Targets in Neuropsychiatric Disorders: The Neuroepigenome
Tremolizzo, L., Rodriguez‐Menendez, V., Conti, E., Zoia, C., Cavaletti, G., & Ferrarese, C. (2014) · Current Pharmaceutical Design · doi:10.2174/13816128113199990535 · Cited by 7 · see citing works
- Authors
- Hathorn, T., Snyder-Keller, A., & Messer, A.
- Affiliations
- Albany Medical College (US)
- New York State Department of Health (US)
- Corresponding author
- Messer, Anne
- Venue
- Neurobiology of Disease
- Publisher
- Elsevier BV
- Published
- 2011-01
- Volume
- 41
- Issue
- 1
- Pages
- 43-50
- ISSN
- 0969-9961 (ISSN-L)
- PMC
- PMC2996046
- OpenAlex
- W2090796483
- Cited by
- 123
- References
- 53
- Citations by year
- 2026: 5 · 2025: 5 · 2024: 8 · 2023: 4 · 2022: 8 · 2021: 9 · 2020: 9 · 2019: 10 · 2018: 7 · 2017: 5 · 2016: 4 · 2015: 8 · 2014: 11 · 2013: 10 · 2012: 12
- FWCI
- 3.87
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Neurobiology of Disease (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institute of Neurological Disorders and Stroke (NS053912)
- National Institutes of Health
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Genetic Neurodegenerative Diseases
- Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Health Sciences › Medicine › Physiology › Lysosomal Storage Disorders Research
- Keywords
- Huntington's disease, nicotinamide, PGC-1α, brain-derived neurotrophic factor, mitochondrial biogenesis, motor impairment, huntingtin aggregation, polyglutamine repeat, energy metabolism, neuroprotection
- MeSH terms
- Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha, Animals, Disease Models, Animal, Female, Humans, Huntington Disease, Male, Mice, Inbred C57BL, Mice, Transgenic, Niacinamide, Transcription Factors, Vitamin B Complex, Trans-Activators, Up-Regulation, Brain-Derived Neurotrophic Factor, Mitochondrial Diseases, Mice
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