Differential Histone Deacetylase mRNA Expression Patterns in Amyotrophic Lateral Sclerosis
Abstract
Histone deacetylases (HDACs) are important regulators of gene expression and cell differentiation. The HDAC inhibitors have recently been considered as potential novel neuroprotective drugs for the treatment of neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS). A major limitation, however, lies in the broad spectrum of action of currently available HDAC inhibitors that may cause a variety of toxic side effects. The mRNA expression levels of the HDAC isoforms HDACs 1 to 11 have previously been characterized in rat brain but have not been studied in human tissue. Using in situ hybridization histochemistry and immunohistochemistry we assessed the distribution and expression levels of HDACs 1to 11 in postmortem ALS and control brain and spinal cord specimens (n = 6 cases each) to determine alterations in the mRNA expression pattern that could provide a basis for disease-specific therapies. We found a reduction of HDAC 11 mRNA and increased HDAC 2 levels in ALS brain and spinal cord compared with controls. A more precise knowledge of the disease-related expression pattern could lead to the development of more specific pharmacotherapeutic approaches.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
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?
The HDAC2-inhibitor structures revealed an overall HDAC2 protein conformation similar to a previously solved HDAC2 structure, albeit at significantly higher resolution.
“The structures revealed an overall HDAC2 protein conformation similar to a previously solved HDAC2 structure, albeit at significantly higher resolution (Table 1 and Fig. 2) (17-19, 31, 33).”
From Histone Deacetylase (HDAC) Inhibitor Kinetic Rate Constants Correlate with Cellular Histone Acetylation but Not Transcription and Cell Viability (2013) · cites this paper as [18]
Cites
HDAC6 rescues neurodegeneration and provides an essential link between autophagy and the UPS.
Pandey, U. B., Nie, Z., Batlevi, Y., McCray, B. A., Ritson, G. P., Nedelsky, N. B., Schwartz, S. L., DiProspero, N. A., Knight, M. A., Schuldiner, O., et al. (2007) · Nature · doi:10.1038/nature05853 · Cited by 1,234 · see citing works
Gao, L., Cueto, M. A., Asselbergs, F., & Atadja, P. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m111871200 · Cited by 744 · see citing works
The histone deacetylase HDAC11 regulates the expression of interleukin 10 and immune tolerance
Villagra, A., Cheng, F., Wang, H.-W., Suarez, I., Glozak, M., Maurin, M., Nguyen, D., Wright, K. L., Atadja, P. W., Bhalla, K., et al. (2009) · Nature Immunology · doi:10.1038/ni.1673 · Cited by 455 · see citing works
Brichta, L. (2003) · Human Molecular Genetics · doi:10.1093/hmg/ddg256 · Cited by 382 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Epigenetic protein families: a new frontier for drug discovery
Arrowsmith, C. H., Bountra, C., Fish, P. V., Lee, K., & Schapira, M. (2012) · Nature Reviews Drug Discovery · doi:10.1038/nrd3674 · Cited by 1,327 · see citing works
Lauffer, B. E. L., Mintzer, R., Fong, R., Mukund, S., Tam, C., Zilberleyb, I., Flicke, B., Ritscher, A., Fedorowicz, G., Vallero, R., et al. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.490706 · Cited by 429 · see citing works
Epigenetic regulation of gene expression in physiological and pathological brain processes
Gräff, J., Kim, D., Dobbin, M. M., & Tsai, L.-H. (2011) · Physiological Reviews · doi:10.1152/physrev.00012.2010 · Cited by 373 · see citing works
Shukla, S., & Tekwani, B. L. (2020) · Frontiers in Pharmacology · doi:10.3389/fphar.2020.00537 · Cited by 314 · see citing works
Figueroa-Romero, C., Guo, K., Murdock, B. J., Paez-Colasante, X., Bassis, C. M., Mikhail, K. A., Raue, K. D., Evans, M. C., Taubman, G. F., McDermott, A. J., et al. (2019) · Disease Models & Mechanisms · doi:10.1242/dmm.041947 · Cited by 94 · see citing works
Rossaert, E., Pollari, E., Jaspers, T., Van Helleputte, L., Jarpe, M., Van Damme, P., De Bock, K., Moisse, M., & Van Den Bosch, L. (2019) · Acta Neuropathologica Communications · doi:10.1186/s40478-019-0750-2 · Cited by 93 · see citing works
The role of altered protein acetylation in neurodegenerative disease
Kabir, F., Atkinson, R., Cook, A. L., Phipps, A. J., & King, A. E. (2023) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2022.1025473 · Cited by 75 · see citing works
Körner, S., Böselt, S., Thau, N., Rath, K. J., Dengler, R., & Petri, S. (2013) · Neurodegenerative Diseases · doi:10.1159/000338048 · Cited by 64 · see citing works
Self-citationBurg, T., Rossaert, E., Moisse, M., Van Damme, P., & Van Den Bosch, L. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms222011224 · Cited by 50 · see citing works
Visualizing epigenetics: Current advances and advantages in HDAC PET imaging techniques
Wang, C., Schroeder, F. A., & Hooker, J. M. (2014) · Neuroscience · doi:10.1016/j.neuroscience.2013.09.018 · Cited by 48 · see citing works
- Authors
- Janssen, C., Schmalbach, S., Boeselt, S., Sarlette, A., Dengler, R., & Petri, S.
- Affiliations
- Medizinische Hochschule Hannover (DE)
- Corresponding author
- Schmalbach, Sonja
- Venue
- Journal of Neuropathology & Experimental Neurology
- Publisher
- Oxford University Press (OUP)
- Published
- 2010-06
- Volume
- 69
- Issue
- 6
- Pages
- 573-581
- ISSN
- 0022-3069 (ISSN-L)
- 1554-6578
- OpenAlex
- W2052141092
- Cited by
- 100
- References
- 4
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 12 · 2023: 7 · 2022: 2 · 2021: 7 · 2020: 10 · 2019: 6 · 2018: 4 · 2017: 7 · 2016: 4 · 2015: 8 · 2014: 4 · 2013: 10 · 2012: 9
- FWCI
- 2.86
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neuropathology & Experimental Neurology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Histone Deacetylase Inhibitors Research
- Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Genetic Neurodegenerative Diseases
- Keywords
- histone deacetylase, amyotrophic lateral sclerosis, HDAC2, HDAC isoforms, spinal cord, brain, neurodegeneration, histone deacetylase inhibitors, neuroprotection, postmortem brain
- MeSH terms
- Adult, Aged, Aged, 80 and over, Amyotrophic Lateral Sclerosis, Brain, Female, Histone Deacetylases, Humans, Immunohistochemistry, Male, Middle Aged, Neurons, RNA, Messenger, Spinal Cord, Gene Expression, Case-Control Studies, In Situ Hybridization
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
