The DOI matches its Crossref record; 53 of the 53 references it cites were found in a registry or an index.
Nicotinamide improves motor deficits and upregulates PGC-1α and BDNF gene expression in a mouse model of Huntington's disease
Open accessAbstract
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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“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
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
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
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
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
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. P., & Aronin, N. (1997) · Science · doi:10.1126/science.277.5334.1990 · Cited by 2,439
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
Dent, S., Denu, J. M., & Allis, C. D. (2001) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.70.1.81 · Cited by 1,906
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
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
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 1,123
Handschin, C., & Spiegelman, B. M. (2006) · Endocrine Reviews · doi:10.1210/er.2006-0037 · Cited by 1,090
Flagged first, then by citations
Cited by
Sorted by citations
Items 101–122 of 122
Machado-Joseph Disease / Spinocerebellar Ataxia Type 3
Nbrega, C., & de Almei, L. P. (2012) · InTech eBooks · doi:10.5772/28576 · Cited by 7
Griffin, S. M., Pickard, M. R., Hawkins, C., Williams, A. C., & Fricker, R. A. (2020) · PLoS ONE · doi:10.1371/journal.pone.0233477 · Cited by 5
Synthesis and Antimicrobial Activity of Newly Synthesized Nicotinamides
Marković, B. A., Marinković, А., Antić‐Stanković, J., Mijatović, S., Cvijetić, I., Simić, M. R., & Arandjelović, I. (2024) · Pharmaceutics · doi:10.3390/pharmaceutics16081084 · Cited by 5
González, E., Contreras, I., & Estrada, J. A. (2014) · Neurología (English Edition) · doi:10.1016/j.nrleng.2013.10.017 · Cited by 4
Coppedè, F., Bosco, P., Fuso, A., & Troen, A. M. (2012) · Current Gerontology and Geriatrics Research · doi:10.1155/2012/926082 · Cited by 5
Immunotherapy on Experimental Models for Huntington’s Disease
Messer, A. C. (2016) · Methods in pharmacology and toxicology · doi:10.1007/978-1-4939-3560-4_10 · Cited by 3
Self-citationRole of AMP-activated protein kinase and sirtuins as antiaging proteins
Ramu, M., Vishal, S. S., & Gogia, N. (2022) · Elsevier eBooks · doi:10.1016/b978-0-323-90235-9.00015-x · Cited by 3
Basso, M. (2012) · InTech eBooks · doi:10.5772/31579 · Cited by 2
González, E., Contreras, I., & Estrada, J. A. (2013) · Neurología · doi:10.1016/j.nrl.2013.10.005 · Cited by 3
Mason, S. (2025) · Frontiers in Neuroscience · doi:10.3389/fnins.2025.1498655 · Cited by 2
Khaksar, Z., & Moradi, H. R. (2026) · The Neuroscience Journal of Shefaye Khatam · doi:10.66224/shefa.14.2.67 · Cited by 2
You, Y., Duan, D., & Xiang, Q. (2026) · Molecular Neurobiology · doi:10.1007/s12035-026-06029-x · Cited by 2
Pathogenesis of Huntington’s Disease: How to Fight Excitotoxicity and Transcriptional Dysregulation
Anglada‐Huguet, M., Vidal-Sancho, L., Cabezas-Llobet, N., Alberch, J., & Xifró, X. (2017) · InTech eBooks · doi:10.5772/66734 · Cited by 2
[Research Progress in Niacinamide in the Prevention and Treatment of Mouth and Systemic Diseases].
Lei, Z.-X., Lin, Y.-W., Li, Y., & Zhou, X. (2023) · PubMed Central · doi:10.12182/20230160105 · Cited by 3
Effects of Insulin on synapse formation and function; A possible role for insulin resistance
Hariharan, M. (2015) · DalSpace (Dalhousie University) · Cited by 1
Huntington Disease and Other Genetic Choreas
Ha, A. D., & Jankovic, J. J. (2011) · Wiley eBooks · doi:10.1002/9781444346183.ch10 · Cited by 1
Therapeutics for Polyglutamine Diseases Through Protein Degradation Pathway: Targeting the Nucleus
Iwata, A. (2015) · Springer eBooks · doi:10.1007/978-4-431-55763-0_23
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) · SSRN Electronic Journal · doi:10.2139/ssrn.4054845
Nicotinamide enhances lipid deposition and thermogenesis in goat brown adipocytes
Ke, J., Suo, L., De, J., Li, D., Dai, X., & Wang, L. (2026) · Domestic Animal Endocrinology · doi:10.1016/j.domaniend.2026.107040
Padole, V. N., & Kulkarni, Y. A. (2026) · Metabolic Brain Disease · doi:10.1007/s11011-026-01948-z
Metadata
- 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 › Genetics (clinical) › 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
