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Nicotinamide Restores Cognition in Alzheimer's Disease Transgenic Mice via a Mechanism Involving Sirtuin Inhibition and Selective Reduction of Thr231-Phosphotau
Open accessAbstract
Memory loss is the signature feature of Alzheimer's disease, and therapies that prevent or delay its onset are urgently needed. Effective preventive strategies likely offer the greatest and most widespread benefits. Histone deacetylase (HDAC) inhibitors increase histone acetylation and enhance memory and synaptic plasticity. We evaluated the efficacy of nicotinamide, a competitive inhibitor of the sirtuins or class III NAD + -dependent HDACs in 3xTg-AD mice, and found that it restored cognitive deficits associated with pathology. Nicotinamide selectively reduces a specific phospho-species of tau (Thr231) that is associated with microtubule depolymerization, in a manner similar to inhibition of SirT1. Nicotinamide also dramatically increased acetylated α-tubulin, a primary substrate of SirT2, and MAP2c, both of which are linked to increased microtubule stability. Reduced phosphoThr231-tau was related to a reduction of monoubiquitin-conjugated tau, suggesting that this posttranslationally modified form of tau may be rapidly degraded. Overexpression of a Thr231-phospho-mimic tau in vitro increased clearance and decreased accumulation of tau compared with wild-type tau. These preclinical findings suggest that oral nicotinamide may represent a safe treatment for AD and other tauopathies, and that phosphorylation of tau at Thr231 may regulate tau stability.
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“Four months of NAM treatment increased the level of p25 2-fold, reduced p-TauThr231 levels, and improved cognitive function in 3xTgAD mice (Green et al., 2008).”
From NAD+ in Brain Aging and Neurodegenerative Disorders (2019) · cites this paper as Green et al., 2008
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“NAD+ augmentation inhibited Tau phosphorylation at different sites (Thr181, Ser202, Thr205, and Thr231) possibly through suppression of cyclin-dependent kinase 5 (Cdk5)-p25 complex activity (Fang et al., 2019; Green et al., 2008).”
From NAD+ in Brain Aging and Neurodegenerative Disorders (2019) · cites this paper as Green et al., 2008
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1 retracted
RETRACTED ARTICLE: A specific amyloid-β protein assembly in the brain impairs memory
Lesné, S., Koh, M. T., Kotilinek, L., Kayed, R., Glabe, C. G., Yang, A., Gallagher, M., & Ashe, K. H. (2006) · Nature · doi:10.1038/nature04533 · Cited by 2,769
RetractedAmyloid oligomers exacerbate tau pathology in a mouse model of tauopathy
Selenica, M.-L. B., Brownlow, M., Jimenez, J. P., Lee, D. C., Pena, G., Dickey, C. A., Gordon, M. N., & Morgan, D. (2013) · Neurodegenerative Diseases · doi:10.1159/000337230 · Cited by 10,359
Resveratrol improves health and survival of mice on a high-calorie diet
Baur, J. A., Pearson, K. J., Price, N. L., Jamieson, H. A., Lerin, C., Kalra, A., Prabhu, V. V., Allard, J. S., Lopez-Lluch, G., Lewis, K., et al. (2006) · Nature · doi:10.1038/nature05354 · Cited by 4,290 · cited 1×
“The sirtuin family of deacetylases is implicated in cellular pathways that influence longevity in yeast, C. elegans, Drosophila, and mammals (Tissenbaum and Guarente, 2001; Anderson et al., 2003; Howitz et al., 2003; Wood et al., 2004; Baur et al., 2006).”
BackgroundTriple-Transgenic Model of Alzheimer’s Disease with Plaques and Tangles
Oddo, S., Caccamo, A., Shepherd, J. D., Murphy, M. P., Golde, T. E., Kayed, R., Metherate, R., Mattson, M. P., Akbari, Y., & LaFerla, F. M. (2003) · Neuron · doi:10.1016/s0896-6273(03)00434-3 · Cited by 4,126 · cited 6×
“By 8 months, somatodendritic accumulation of phospho- and non-phosphotau also occurs in the hippocampus and amygdala, but not the cortex (Oddo et al., 2003).”
BackgroundMethodInfluentialSelf-citationSmall molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan
Howitz, K. T., Bitterman, K. J., Cohen, H. Y., Lamming, D. W., Lavu, S., Wood, J. G., Zipkin, R. E., Chung, P., Kisielewski, A., Zhang, L.-L., et al. (2003) · Nature · doi:10.1038/nature01960 · Cited by 3,796
A new one-trial test for neurobiological studies of memory in rats. 1: behavioral data
Ennaceur, A., & Delacour, J. (1988) · Behavioural Brain Research · doi:10.1016/0166-4328(88)90157-x · Cited by 3,223 · cited 1×
“Kim N. Green,1 Joan S. Steffan,2 Hilda Martinez-Coria,1 Xuemin Sun,3 Steven S. Schreiber,3,5 Leslie Michels Thompson,1,2,4 and Frank M. LaFerla1”
BackgroundDent, S., Denu, J. M., & Allis, C. D. (2001) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.70.1.81 · Cited by 1,906 · cited 2×
“Acetylation of histones and nonhistone transcription factors plays an important role in regulating chromatin condensation and gene transcription (Roth et al., 2001).”
BackgroundReducing Endogenous Tau Ameliorates Amyloid ß-Induced Deficits in an Alzheimer's Disease Mouse Model
Roberson, E. D., Scearce-Levie, K., Palop, J. J., Yan, F., Cheng, I. H., Wu, T., Gerstein, H., Yu, G.-Q., & Mucke, L. (2007) · Science · doi:10.1126/science.1141736 · Cited by 1,892
Sirtuin activators mimic caloric restriction and delay ageing in metazoans
Wood, J. G., Rogina, B., Lavu, S., Howitz, K., Helfand, S. L., Tatar, M., & Sinclair, D. (2004) · Nature · doi:10.1038/nature02789 · Cited by 1,868 · cited 1×
“The sirtuin family of deacetylases is implicated in cellular pathways that influence longevity in yeast, C. elegans, Drosophila, and mammals (Tissenbaum and Guarente, 2001; Anderson et al., 2003; Howitz et al., 2003; Wood et al., 2004; Baur et al., 2006).”
BackgroundIncreased dosage of a sir-2 gene extends lifespan in Caenorhabditis elegans
Tissenbaum, H. A., & Guarente, L. (2001) · Nature · doi:10.1038/35065638 · Cited by 1,603 · cited 1×
“The sirtuin family of deacetylases is implicated in cellular pathways that influence longevity in yeast, C. elegans, Drosophila, and mammals (Tissenbaum and Guarente, 2001; Anderson et al., 2003; Howitz et al., 2003; Wood et al., 2004; Baur et al., 2006).”
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Items 101–200 of 410
Epigenetic Changes in Alzheimer’s Disease: DNA Methylation and Histone Modification
Plano, L. M. D., Saitta, A., Oddo, S., & Caccamo, A. (2024) · Cells · doi:10.3390/cells13080719 · Cited by 93
“The authors reported that this experimental paradigm prevented memory deficits while decreasing tau pathology ([112]).”
BackgroundFerland‐Beckham, C., & Schrader, L. A. (2010) · Neuroscience · doi:10.1016/j.neuroscience.2010.10.077 · Cited by 89
Biella, G., Fusco, F., Nardo, E., Bernocchi, O., Colombo, A. V., Lichtenthaler, S. F., Forloni, G., & Albani, D. (2016) · Journal of Alzheimer s Disease · doi:10.3233/jad-151135 · Cited by 82
“[35, 36].”
BackgroundAntioxidant Alternatives in the Treatment of Amyotrophic Lateral Sclerosis: A Comprehensive Review
Carrera‐Juliá, S., Moreno, M. L., Barrios, C., Ortí, J. E. D. L. R., & Drehmer, E. (2020) · Frontiers in Physiology · doi:10.3389/fphys.2020.00063 · Cited by 87
Metabolism and metabolomics of opiates: A long way of forensic implications to unravel
Dinis‐Oliveira, R. J. (2018) · Journal of Forensic and Legal Medicine · doi:10.1016/j.jflm.2018.12.005 · Cited by 82
Jia, Q., Deng, Y., & Qing, H. (2014) · BioMed Research International · doi:10.1155/2014/837157 · Cited by 84
“Nicotinamide, the precursor of coenzyme NAD+, reduces phosphorylated tau and protects microtubules stabilization in mouse model [125].”
BackgroundPrasad, K. N. (2016) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2016.01.002 · Cited by 83
Berberine: A Plant-derived Alkaloid with Therapeutic Potential to Combat Alzheimer’s disease
Singh, A. K., Singh, S. K., Nandi, M. K., Mishra, G., Maurya, A., Rai, A., Rai, G. K., Awasthi, R., Sharma, B., & Kulkarni, G. T. (2019) · Central Nervous System Agents in Medicinal Chemistry · doi:10.2174/1871524919666190820160053 · Cited by 79
Histone Deacetylase Inhibitors and Neurodegenerative Disorders: Holding the Promise
Mai, A., Rotili, D., Valente, S., & Kazantsev, A. G. (2009) · Current Pharmaceutical Design · doi:10.2174/138161209789649349 · Cited by 79
Does Huntingtin play a role in selective macroautophagy?
Steffan, J. S. (2010) · Cell Cycle · doi:10.4161/cc.9.17.12718 · Cited by 81
Self-citationDisease-modifying drugs in Alzheimer's disease
Scarpini, E. A., Galimberti, D., & Ghezzi, L. (2013) · Drug Design Development and Therapy · doi:10.2147/dddt.s41431 · Cited by 74
Sirtuin 1 overexpression mice show a reference memory deficit, but not neuroprotection
Kakefuda, K., Fujita, Y., Oyagi, A., Hyakkoku, K., Kojima, T., Umemura, K., Tsuruma, K., Shimazawa, M., Ito, M., Nozawa, Y., et al. (2009) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2009.07.119 · Cited by 75
Sildenafil ameliorates cognitive deficits and tau pathology in a senescence-accelerated mouse model
Orejana, L., Barros-Miñones, L., Jordán, J., Puerta, E., & Aguirre, N. (2011) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2011.03.018 · Cited by 73
CDK5 activator protein p25 preferentially binds and activates GSK3β
Chow, H., Guo, D. S., Zhou, J., Zhang, G.-Y., Li, H., Herrup, K., & Zhang, J. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1402627111 · Cited by 78
“The effect of aberrant activity of GSK3β toward tau can also be seen in the brains of various mouse models of Alzheimer’s disease in which the levels of p25 have been shown to be increased (46, 47).”
BackgroundDiverse therapeutic efficacies and more diverse mechanisms of nicotinamide
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 73
Chandramowlishwaran, P., Vijay, A., Abraham, D., Li, G., Mwangi, S. M., & Srinivasan, S. (2020) · Frontiers in Neuroscience · doi:10.3389/fnins.2020.614331 · Cited by 74
“…has shown to provide neuroprotective effects in various animal models of AD by reducing amyloid plaque formation and neurofibrillary tau pathology ( Chen et al., 2005; Qin et al., 2006; Kim et al., 2007; Green et al., 2008; Karuppagounder et al., 2009; Min et al., 2010; Vingtdeux et al., 2010).”
BackgroundLow HDL cholesterol is associated with lower gray matter volume in cognitively healthy adults
Ward (2010) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2010.00029 · Cited by 77
Srivastava, S., & Haigis, M. C. (2011) · Current Pharmaceutical Design · doi:10.2174/138161211798072526 · Cited by 70
Cuadra, I. A., Cabañas, A., Cheda, J. A. R., Martinez-Casado, F. J., & Pando, C. (2015) · Journal of CO2 Utilization · doi:10.1016/j.jcou.2015.11.006 · Cited by 70
Dietary natural products as epigenetic modifiers in aging-associated inflammation and disease
Evans, L. W., Stratton, M. S., & Ferguson, B. S. (2020) · Natural Product Reports · doi:10.1039/c9np00057g · Cited by 71
Gal, J., Bang, Y., & Choi, H. J. (2012) · Neurochemistry International · doi:10.1016/j.neuint.2012.07.010 · Cited by 68
“Because HDAC inhibitors appeared to confer significant neuroprotection in experimental models of proteinopathy-dependent neurodegenerative diseases (Green et al., 2008), we first determined whether SIRT2 played a role in protein clearance in neuronal cells.”
BackgroundTeijido, Ó., & Cacabelos, R. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19103199 · Cited by 69
“This compound improves the stability of microtubules by reducing phosphorylated tau (at Thr231 level) and restored cognitive deficits in triple transgenic 3xTg-AD mice [195].”
BackgroundThe Application of Nanotechnology for the Diagnosis and Treatment of Brain Diseases and Disorders
Ngowi, E. E., Wang, Y., Qian, L., Helmy, Y. A. S. H., Anyomi, B. K., Li, T., Zheng, M., Jiang, E., Duan, S., Wei, J., et al. (2021) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2021.629832 · Cited by 68
Responses in the brain proteome of Atlantic cod (Gadus morhua) exposed to methylmercury
Berg, K., Puntervoll, P., Valdersnes, S., & Goksøyr, A. (2010) · Aquatic Toxicology · doi:10.1016/j.aquatox.2010.07.008 · Cited by 64
“…and possibly axon degeneration, since nicotinamide has recently been implicated in increased microtubule stability through e.g. increased acetylation of alpha tubulin, and has been shown to restore cognition in a mouse model of the neurodegenerative disease Alzheimer’s disease (Green et al., 2008).”
Erburu, M. M., Muñoz-Cobo, I., Diaz-Perdigón, T., Mellini, P., Suzuki, T., Puerta, E., & Tordera, R. M. (2017) · Neuropharmacology · doi:10.1016/j.neuropharm.2017.01.033 · Cited by 64
“Interestingly, selective SIRT2 inhibitors are effective at reducing tau phosphorylation (Green et al., 2008), α-synuclein toxicity (Outeiro et al.”
Kelly, G. S. (2010) · PubMed · Cited by 63
Silva, D. F., Esteves, A. R., Arduíno, D. M., Oliveira, C. R., & Cardoso, S. M. (2011) · Journal of Alzheimer s Disease · doi:10.3233/jad-2011-110423 · Cited by 61
Vandal, M., White, P. J., Tournissac, M., Tremblay, C., St‐Amour, I., Drouin‐Ouellet, J., Bousquet, M., Traversy, M.-T., Planel, E., Marette, A., et al. (2016) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2016.03.024 · Cited by 64
Alzheimer’s Disease – The Past, the Present and the Future
Botchway, B. O. A. (2017) · Science Journal of Clinical Medicine · doi:10.11648/j.sjcm.20170601.11 · Cited by 60
After the grape rush: Sirtuins as epigenetic drug targets in neurodegenerative disorders
Huber, K., & Superti‐Furga, G. (2011) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2011.01.018 · Cited by 60
Current Trends in Sirtuin Activator and Inhibitor Development
Bursch, K. L., Goetz, C. J., & Smith, B. C. (2024) · Molecules · doi:10.3390/molecules29051185 · Cited by 60
“This inspired the use of a cell-free translation and peptide screening platform to generate peptides containing trifluoroacetyl-lysine warheads as Sirt2 inhibitors [239].”
BackgroundMethodInfluentialSIRT1 as a therapeutic target for Alzheimer’s disease
Wong, S. Y., & Tang, B. L. (2016) · Reviews in the Neurosciences · doi:10.1515/revneuro-2016-0023 · Cited by 59
Impaired Mitophagy and Protein Acetylation Levels in Fibroblasts from Parkinson’s Disease Patients
Yakhine-Diop, S. M. S., Niso-Santano, M., Rodríguez-Arribas, M., Gómez-Sánchez, R., Martínez-Chacón, G., Uribe-Carretero, E., Navarro-García, J. A., Ruiz-Hurtado, G., Aiastui, A., Cooper, J. M., et al. (2019) · Molecular Neurobiology · doi:10.1007/s12035-018-1206-6 · Cited by 57
Harrison, I. F., Powell, N. M., & Dexter, D. T. (2018) · Journal of Neurochemistry · doi:10.1111/jnc.14599 · Cited by 59
Molecular mechanisms of mitophagy and its roles in neurodegenerative diseases
Li, X., Huang, L., Lan, J., Feng, X., Li, P., Wu, L., & Peng, Y. (2021) · Pharmacological Research · doi:10.1016/j.phrs.2020.105240 · Cited by 57
Nikseresht, S., Khodagholi, F., & Ahmadiani, A. (2019) · Journal of Cellular Physiology · doi:10.1002/jcp.27055 · Cited by 58
Nicotinamide Augments the Anti-Inflammatory Properties of Resveratrol through PARP1 Activation
Yanez, M., Jhanji, M., Murphy, K. P., Gower, R. M., Sajish, M., & Jabbarzadeh, E. (2019) · Scientific Reports · doi:10.1038/s41598-019-46678-8 · Cited by 61
Sirtuin 2 (SIRT2): Confusing Roles in the Pathophysiology of Neurological Disorders
Chen, X., Lu, W., & Wu, D. (2021) · Frontiers in Neuroscience · doi:10.3389/fnins.2021.614107 · Cited by 57
SIRT1 gene, schizophrenia and bipolar disorder in the Japanese population: an association study
Kishi, T., Fukuo, Y., Kitajima, T., Okochi, T., Yamanouchi, Y., Kinoshita, Y., Kawashima, K., Inada, T., Kunugi, H., Kato, T., et al. (2010) · Genes Brain & Behavior · doi:10.1111/j.1601-183x.2010.00661.x · Cited by 58
“Several investigations have suggested that SIRT1 is related to dopaminergic neural transmission (Green et al. 2008; Liu et al. 2009).”
BackgroundCalcium in the initiation, progression and as an effector of Alzheimer’s disease pathology
Green, K. N. (2009) · Journal of Cellular and Molecular Medicine · doi:10.1111/j.1582-4934.2009.00861.x · Cited by 56
“We have also demonstrated recently that treatment of 3 Tg-AD mice with the sirtuin inhibitor nicotinamide prevents cognitive deficits by removing phosphorylated at threonine 231, with no effects on A [84].”
BackgroundSelf-citationSorial, M. E. S., & Sayed, N. S. E. (2017) · Naunyn-Schmiedeberg s Archives of Pharmacology · doi:10.1007/s00210-017-1357-4 · Cited by 58
Nandave, M., Acharjee, R., Bhaduri, K., Upadhyay, J., Rupanagunta, G. P., & Ansari, M. N. (2023) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2023.124581 · Cited by 56
Dong, Y., Digman, M. A., & Brewer, G. J. (2019) · GeroScience · doi:10.1007/s11357-019-00052-8 · Cited by 54
Wang, X., He, H., Xiong, X., Zhou, S., Wang, W., Feng, L., Han, R., & Xie, C. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.668491 · Cited by 56
Herrera‐Marschitz, M., Morales, P., Leyton, L., Bustamante, D., Klawitter, V., Espina-Marchant, P., Allende-Castro, C., Lisboa, F., Cunich, G., Jara-Cavieres, A., et al. (2010) · Neurotoxicity Research · doi:10.1007/s12640-010-9208-9 · Cited by 54
“Nevertheless, the mechanisms explaining the protection provided by nicotinamide have to be further investigated, including histone deacetylation, a mechanism proposed for the recent introduction of nicotinamide as a treatment for Alzheimer’s disease and other taupathies (Green et al. 2008).”
BackgroundInsights into Lysine Deacetylation of Natively Folded Substrate Proteins by Sirtuins
Knyphausen, P., de Boor, S., Kuhlmann, N., Scislowski, L., Extra, A., Baldus, L., Schacherl, M., Baumann, U., Neundorf, I., & Lammers, M. (2016) · Journal of Biological Chemistry · doi:10.1074/jbc.m116.726307 · Cited by 52
Biochemical pathways that regulate acetyltransferase and deacetylase activity in mammalian cells
Mellert, H. S., & McMahon, S. B. (2009) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2009.06.010 · Cited by 52
Lloret, A., & Beal, M. F. (2019) · Neurochemical Research · doi:10.1007/s11064-019-02809-1 · Cited by 52
Pasco, M. Y., Rotili, D., Altucci, L., Farina, F., Rouleau, G. A., Mai, A., & Néri, C. (2009) · Journal of Medicinal Chemistry · doi:10.1021/jm9013345 · Cited by 53
Environmental factors in the development and progression of late-onset Alzheimer’s disease
Wainaina, M. N., Chen, Z., & Zhong, C. (2014) · Neuroscience Bulletin · doi:10.1007/s12264-013-1425-9 · Cited by 53
“[219] Green KN, Steffan JS, Martinez-Coria H, Sun X, Schreiber SS, Thompson LM, et al.”
BackgroundBevill, M. J., Vlahova, P. I., & Smit, J. P. (2014) · Crystal Growth & Design · doi:10.1021/cg4019037 · Cited by 50
Histone Deacetylase Inhibitors: A Therapeutic Key in Neurological Disorders?
Ziemka‐Nałęcz, M., Jaworska, J., Sypecka, J., & Zalewska, T. (2018) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/nly073 · Cited by 53
“impairments and decreased tau pathology without any effect on b-amyloid load or production (46).”
BackgroundEpigenetic mechanisms of amyloid-β production in anisomycin-treated SH-SY5Y cells
Guo, X., Wu, X., Ren, L.-N., Liu, G., & Li, L. (2011) · Neuroscience · doi:10.1016/j.neuroscience.2011.07.012 · Cited by 48
Epigenetic Basis of Neuronal and Synaptic Plasticity
Karpova, N. N., Sales, A. J., & Joca, S. R. L. (2016) · Current Topics in Medicinal Chemistry · doi:10.2174/1568026616666160414124628 · Cited by 51
Roles of NAD + in Health and AgingPreprint
Lautrup, S., Hou, Y., Fang, E. F., & Bohr, V. A. (2023) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a041193 · Cited by 53
Jansen, D., Zerbi, V., Arnoldussen, I. A. C., Wiesmann, M., Rijpma, A., Fang, X. T., Dederen, P. J. W. C., Mutsaers, M. P. C., Broersen, L. M., Lütjohann, D., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0075393 · Cited by 47
Status and future directions of clinical trials in Alzheimer's disease
Plascencia‐Villa, G., & Perry, G. L. (2020) · International review of neurobiology · doi:10.1016/bs.irn.2020.03.022 · Cited by 49
Revisiting the Role of Vitamins and Minerals in Alzheimer’s Disease
Shah, H., Dehghani, F., Ramezan, M., Gannaban, R. B., Haque, Z. F., Rahimi, F. C., Abbasi, S., & Shin, A. C. (2023) · Antioxidants · doi:10.3390/antiox12020415 · Cited by 48
“Green and colleagues examined the efficacy of nicotinamide in restoring cognitive functions associated with AD pathology in 3xTg-AD mice [47].”
BackgroundMitochondrial Targets for Pharmacological Intervention in Human Disease
Malty, R. H., Jessulat, M., Jin, K., Musso, G. A., Vlasblom, J., Phanse, S., Zhang, Z., & Babu, M. (2014) · Journal of Proteome Research · doi:10.1021/pr500813f · Cited by 45
Restoring the epigenome in Alzheimer's disease: advancing HDAC inhibitors as therapeutic agents
Pereira, M. S., Cruz, M. T., Fortuna, A. C., & Bicker, J. (2024) · Drug Discovery Today · doi:10.1016/j.drudis.2024.104052 · Cited by 47
Ghosh, D., LeVault, K. R., & Brewer, G. J. (2013) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2013.06.023 · Cited by 43
“…increase GSH and decrease ROS in old neurons Nicotinamide is a direct NADþ precursor which when administered through drinking water increases NADH and NADPH in the striatum and thalamus of mouse brain (Klaidman et al., 2001) or improves cognitive deficits in 3xTg-AD mice (Green et al., 2008).”
InfluentialMorales, P., Simola, N., Bustamante, D., Lisboa, F., Fiedler, J. L., Gebicke‐Haerter, P. J., Morelli, M., Tasker, R. A., & Herrera‐Marschitz, M. (2009) · Experimental Brain Research · doi:10.1007/s00221-009-2103-z · Cited by 44
“nicotinamide as a treatment of Alzheimer’s disease and other taupathies (Green et al. 2008).”
BackgroundDrug Repositioning for Alzheimer’s Disease: Finding Hidden Clues in Old Drugs
Ihara, M., & Saitô, S. (2020) · Journal of Alzheimer s Disease · doi:10.3233/jad-200049 · Cited by 45
“Nicotinamide inhibited histone deacetylase and phosphorylated tau in a mouse model of AD [65].”
Luo, P., Yan, H., Chen, X., Zhang, Y., Zhao, Z., Cao, J., Zhu, Y., Du, J., Xu, Z., Zhang, X., et al. (2020) · Cell Research · doi:10.1038/s41422-020-0309-6 · Cited by 44
The role of mitochondrial disturbances in Alzheimer, Parkinson and Huntington diseases
Carvalho, C., Correia, S. C., Cardoso, S., Plácido, A. I., Candeias, E., Duarte, A. I., & Moreira, P. I. (2015) · Expert Review of Neurotherapeutics · doi:10.1586/14737175.2015.1058160 · Cited by 45
“On one hand, increased NAD biosynthesis leads to SIRT1 activation increasing mitochondrial biogenesis and protecting axons against degeneration [229] and, on the other hand, it has been demonstrated that inhibitors of NAD-dependent class III histone deacetylases, the sirtuin family, where SIRT1 is included, are able t…”
BackgroundLiu, R., Lei, J. X., Luo, C., Lan, X., Chi, L., Deng, P., Lei, S., Ghribi, O., & Liu, Q. Y. (2012) · Neurobiology of Disease · doi:10.1016/j.nbd.2011.12.007 · Cited by 42
Epigenetic modification is linked to Alzheimer's disease: is it a maker or a marker?
Lee, J.-H., & Ryu, H. (2010) · BMB Reports · doi:10.5483/bmbrep.2010.43.10.649 · Cited by 43
Cao, Y., Yan, Z., Zhou, T., & Wang, G. (2017) · Journal of Diabetes Research · doi:10.1155/2017/7121827 · Cited by 45
“Nicotinamide, an inhibitor of SIRT1, has been shown to attenuate cognitive deficits of 3xTg-AD mice via inhibition of SIRT1 and phosphorylation of tau [49].”
BackgroundLardenoije, R., van den Hove, D., Havermans, M., van Casteren, A., Le, K. X., Palmour, R., Lemere, C. A., & Rutten, B. P. F. (2017) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2017.11.002 · Cited by 42
“Nevertheless, treatment with HDAC inhibitors is also able to improve cognition in the 3xTg-AD mice (Green et al., 2008; Sung et al., 2013).”
BackgroundNoh, H., & Seo, H. (2014) · Neuroscience · doi:10.1016/j.neuroscience.2014.02.012 · Cited by 41
“Nicotinamide increased histone acetylation and enhanced memory and synaptic plasticity (Green et al., 2008).”
Cieślik, M., Czapski, G. A., & Strosznajder, J. B. (2015) · PLoS ONE · doi:10.1371/journal.pone.0137193 · Cited by 43
Emerging Roles of Sirtuins in Ischemic Stroke
She, D. T., Jo, D., & Arumugam, T. V. (2017) · Translational Stroke Research · doi:10.1007/s12975-017-0544-4 · Cited by 41
Williams, A. C., Hill, L. J., & Ramsden, D. B. (2012) · Current Gerontology and Geriatrics Research · doi:10.1155/2012/302875 · Cited by 42
“…and the tolerogenic pathway both for microbes and cancer and contains some potential neurotoxins and is disturbed in many degenerative diseases: enough NAD from vitamin B3 sources means less toleration of symbionts and at the extreme immune intolerance and allergic disorders [194, 195].”
BackgroundRehman, 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
“NAM also showed neuroprotective properties against Alzheimer’s disease [58], Huntington’s disease [59], hypoxic ischemia [19], traumatic brain injuries, headache, and other psychiatric disorders [60].”
BackgroundDrug pipeline in neurodegeneration based on transgenic mice models of Alzheimer's disease
Li, C., Ebrahimi, A., & Schluesener, H. J. (2012) · Ageing Research Reviews · doi:10.1016/j.arr.2012.09.002 · Cited by 44
5-((3-Amidobenzyl)oxy)nicotinamides as Sirtuin 2 Inhibitors
Ai, T., Wilson, D. J., More, S. S., Xie, J., & Chen, L. (2016) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.5b01376 · Cited by 39
Hyun, D. H., Mughal, M. R., Yang, H., Lee, J. H., Ko, E. J., Hunt, N. D., de Cabo, R., & Mattson, M. P. (2010) · Experimental Neurology · doi:10.1016/j.expneurol.2010.07.020 · Cited by 39
Skawratananond, S., Xiong, D. X., Zhang, C., Tonk, S. S., Pinili, A., Delacruz, B., Pham, P., Smith, S. C., Navab, R., & Reddy, P. H. (2025) · Ageing Research Reviews · doi:10.1016/j.arr.2025.102732 · Cited by 41
Nicotinamide and neurocognitive function
Rennie, G. E., Chen, A. C., Dhillon, H. M., Vardy, J. L., & Damian, D. L. (2014) · Nutritional Neuroscience · doi:10.1179/1476830514y.0000000112 · Cited by 40
Glial epigenetics in neuroinflammation and neurodegeneration
Staszewski, O., & Prinz, M. (2014) · Cell and Tissue Research · doi:10.1007/s00441-014-1815-y · Cited by 39
Hoos, M. D., Richardson, B. M., Foster, M. W., Everhart, A. L., Thompson, J. W., Moseley, M. A., & Colton, C. A. (2013) · Journal of Proteome Research · doi:10.1021/pr4005103 · Cited by 37
Ferland‐Beckham, C., Hawley, W. R., Puckett, R. E., Wineberg, K., Lubin, F. D., Dohanich, G. P., & Schrader, L. A. (2013) · Biological Psychiatry · doi:10.1016/j.biopsych.2013.07.029 · Cited by 37
“Nicotinamide, a sirtuin inhibitor, prevented memory impairment on the Morris water maze spatial task in a transgenic model for Alzheimer’s associated with cognitive decline, further implicating a role for sirtuins in hippocampusdependent memory formation (37).”
Epigenetic drugs in Alzheimer’s disease
Cuadrado‐Tejedor, M., Oyarzábal, J., Pascual‐Lucas, M., Franco, R., & García‐Osta, A. (2013) · BioMolecular Concepts · doi:10.1515/bmc-2013-0012 · Cited by 37
Nutrition: Review on the Possible Treatment for Alzheimer’s Disease
Botchway, B. O. A., Moore, M. K., Akinleye, F. O., Iyer, I. C., & Fang, M. (2017) · Journal of Alzheimer s Disease · doi:10.3233/jad-170874 · Cited by 38
Nmnat2 Attenuates Tau Phosphorylation Through Activation of PP2A
Cheng, X., Zhao, K.-P., Jiang, X., Du, L., Li, X., Ma, Z., Yao, J., Luo, Y., Duan, D.-X., Wang, J., et al. (2013) · Journal of Alzheimer s Disease · doi:10.3233/jad-122173 · Cited by 38
“The activity of PP2A is significantly decreased in the brains of AD patients [13], and the downregulation of PP2A results in tau hyperphosphorylation at multiple AD-related sites including Thr205, Thr231, and Ser262, which leads to dysfunction of tau proteins [49–53].”
Imaging Epigenetics in Alzheimer’s Disease
Lista, S., Garaci, F. G., Toschi, N., & Hampel, H. J. (2013) · Current Pharmaceutical Design · doi:10.2174/13816128113199990370 · Cited by 36
“The oral administration of nicotinamide, a class III HDAC inhibitor, reverses cognitive deficits and decreases the level of tau phosphorylation in the 3xTg-AD mouse model [151].”
BackgroundZhong, T., Guo, Q., Zou, W., Zhu, X., Song, Z., Sun, B., He, X., & Yang, Y. (2015) · PLoS ONE · doi:10.1371/journal.pone.0125815 · Cited by 37
“For instance, Green and coworkers[56] reported that nicotinamide’s inhibitory effect on class III NAD(+)-dependent HDACs rescued cognitive deficits in a transgenic mouse model of AD through a mechanism involving the increased acetylation alpha-tubulin and MAP2c and reduced Thr231-phospho-tau.”
BackgroundCastello, N. A., Green, K. N., & LaFerla, F. M. (2012) · PLoS ONE · doi:10.1371/journal.pone.0039566 · Cited by 36
“ELISA detection of soluble and insoluble Ab40 and Ab42 levels was conducted as described previously [38].”
MethodSelf-citationH. Swerdlow, R. (2011) · Current Pharmaceutical Design · doi:10.2174/138161211798072535 · Cited by 35
Sirtuins in Neurodegenerative Diseases: A Biological-Chemical Perspective
Raghavan, A., & Shah, Z. A. (2011) · Neurodegenerative Diseases · doi:10.1159/000329724 · Cited by 36
Posterity of nanoscience as lipid nanosystems for Alzheimer's disease regression
Naser, S. S., Singh, D., Preetam, S., Kishore, S., Kumar, L., Nandi, A., Simnani, F. Z., Choudhury, A., Sinha, A., Mishra, Y. K., et al. (2023) · Materials Today Bio · doi:10.1016/j.mtbio.2023.100701 · Cited by 37
ST101 induces a novel 17kDa APP cleavage that precludes Aβ generation in vivo
Green, K. N., Khashwji, H., Estrada, T., & LaFerla, F. M. (2011) · Annals of Neurology · doi:10.1002/ana.22325 · Cited by 34
“were measured using a sensitive sandwich ELISA system as previously described.(13) For Ab readings from cynomolgus monkey hippocampal lysates, commercial Ab40 and Ab42 kits were”
MethodSelf-citationMetabolism, longevity and epigenetics
Cosentino, C., & Mostoslavsky, R. (2013) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-013-1295-3 · Cited by 35
“A different study has suggested instead that SIRT1 inhibition in mice restores cognition in AD by stabilizing tau protein [136].”
Late-onset dementia: a mosaic of prototypical pathologies modifiable by diet and lifestyle
Mattson, M. P. (2015) · npj Aging and Mechanisms of Disease · doi:10.1038/npjamd.2015.3 · Cited by 34
Lane, R. F., Shineman, D. W., Steele, J., Lee, L. H., & Fillit, H. M. (2012) · Advances in pharmacology · doi:10.1016/b978-0-12-394816-8.00007-6 · Cited by 35
Ishihara, S., Hattori, Y., & Otsuka, M. (2019) · Spectrochimica Acta Part A Molecular and Biomolecular Spectroscopy · doi:10.1016/j.saa.2019.117142 · Cited by 33
Genetic Variants and Oxidative Stress in Alzheimer’s Disease
Kowalska, M., Wize, K., Prendecki, M., Lianeri, M., Kozubski, W. P., & Dorszewska, J. (2020) · Current Alzheimer Research · doi:10.2174/1567205017666200224121447 · Cited by 34
Potential of chromatin modifying compounds for the treatment of Alzheimer's disease
Karagiannis, T. C., & Ververis, K. (2012) · Pathobiology of Aging & Age-related Diseases · doi:10.3402/pba.v2i0.14980 · Cited by 34
“Hyperacetylation of a-tubulin was also observed (60).”
BackgroundInfluentialHAT and HDAC: Enzyme with Contradictory Action in Neurodegenerative Diseases
Singh, R., Rathore, A. S., Dilnashin, H., Keshri, P. K., Gupta, N. K., Satyaprakash, S. A., Zahra, W., Singh, S., & Singh, S. P. (2024) · Molecular Neurobiology · doi:10.1007/s12035-024-04115-6 · Cited by 31
Jansen, D., Zerbi, V., Janssen, C. I. F., van Rooij, D., Zinnhardt, B., Dederen, P. J. W. C., Wright, A. J., Broersen, L. M., Lütjohann, D., Heerschap, A., et al. (2013) · Brain Structure and Function · doi:10.1007/s00429-013-0606-7 · Cited by 35
“In addition, transgenic mice fed vitamin E (Conte et al. 2004) or vitamin B3 (Green et al. 2008) showed normalized escape latency in the water maze.”
Background
Metadata
- Authors
- Green, K. N., Steffan, J. S., Martinez-Coria, H., Sun, X., Schreiber, S. S., Thompson, L. M., & LaFerla, F. M.
- Affiliations
- University of California, Irvine (US)
- Corresponding author
- LaFerla, Frank M.
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2008-11-05
- Volume
- 28
- Issue
- 45
- Pages
- 11500-11510
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC2617713
- OpenAlex
- W2089740883
- Cited by
- 404
- References
- 59
- Citations by year
- 2026: 9 · 2025: 20 · 2024: 25 · 2023: 24 · 2022: 18 · 2021: 23 · 2020: 23 · 2019: 21 · 2018: 21 · 2017: 28 · 2016: 18 · 2015: 18 · 2014: 29 · 2013: 27 · 2012: 28
- FWCI
- 16.52
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- Funders
- Alzheimer's Drug Discovery Foundation
- National Institutes of Health
- National Institute on Aging (AG0212982, R01AG021982)
- National Institute of Neurological Disorders and Stroke (R01NS052789, NS52789)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- nicotinamide, Alzheimer's disease, sirtuins, SIRT1, SIRT2, tau phosphorylation, acetylated alpha-tubulin, microtubule stability, histone deacetylase inhibition, 3xTg-AD mice, cognitive impairment, tau clearance, tauopathy, memory loss
- MeSH terms
- Alzheimer Disease, Animals, Behavior, Animal, Butyrates, Cell Line, Transformed, Cognition Disorders, Disease Models, Animal, Enzyme Inhibitors, Humans, Mice, Inbred C57BL, Mice, Transgenic, Microtubule-Associated Proteins, Mutation, Niacinamide, Peptide Fragments, Phosphorylation, Threonine, Time Factors, Transfection, Tubulin, Vitamin B Complex, Amyloid beta-Peptides, Amyloid beta-Protein Precursor, tau Proteins, Maze Learning, Sirtuins, Immunoprecipitation, Mice, Presenilin-1
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