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Understanding the Role of Histone Deacetylase and their Inhibitors in Neurodegenerative Disorders: Current Targets and Future Perspective
Open accessAbstract
Neurodegenerative diseases are a group of pathological conditions that cause motor incordination (jerking movements), cognitive and memory impairments result from degeneration of neurons in a specific area of the brain. Oxidative stress, mitochondrial dysfunction, excitotoxicity, neuroinflammation, neurochemical imbalance and histone deacetylase enzymes (HDAC) are known to play a crucial role in neurodegeneration. HDAC is classified into four categories (class I, II, III and class IV) depending upon their location and functions. HDAC1 and 2 are involved in neurodegeneration, while HDAC3-11 and class III HDACs are beneficial as neuroprotective. HDACs are localized in different parts of the brain- HDAC1 (hippocampus and cortex), HDAC2 (nucleus), HDAC3, 4, 5, 7 and 9 (nucleus and cytoplasm), HDAC6 & HDAC7 (cytoplasm) and HDAC11 (Nucleus, cornus ammonis 1 and spinal cord). In pathological conditions, HDAC up-regulates glutamate, phosphorylation of tau, and glial fibrillary acidic proteins while down-regulating BDNF, Heat shock protein 70 and Gelsolin. Class III HDACs are divided into seven sub-classes (SIRT1-SIRT7). Sirtuins are localized in the different parts of the brain and neuron -Sirt1 (nucleus), Sirt2 (cortex, striatum, hippocampus and spinal cord), Sirt3 (mitochondria and cytoplasm), Sirt4, Sirt5 & Sirt6 (mitochondria), Sirt7 (nucleus) and Sirt8 (nucleolus). SIRTs (1, 3, 4, and 6) are involved in neuronal survival, proliferation and modulating stress response, and SIRT2 is associated with Parkinsonism, Huntington's disease and Alzheimer's disease, whereas SIRT6 is only associated with Alzheimer's disease. In this critical review, we have discussed the mechanisms and therapeutic targets of HDACs that would be beneficial for the management of neurodegenerative disorders.
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“HDAC inhibitors often display limited isoform selectivity and off-target activity, which constrains their translational potential in the nervous system (Kumar et al., 2022).”
From Histone modifications and depression: epigenetic mechanisms, therapeutic targets, and translational outlook (2026) · cites this paper as Kumar et al., 2022
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“HDAC6, a predominantly cytoplasmic deacetylase, regulates microtubule dynamics and autophagic flux (Kumar et al., 2022).”
From Histone modifications and depression: epigenetic mechanisms, therapeutic targets, and translational outlook (2026) · cites this paper as Kumar et al., 2022
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“HDAC inhibitors can enhance histone acetylation and ameliorate cognitive impairments in various AD models, and HDAC inhibition has been recognized as an attractive therapeutic strategy for AD [4, 5, 7].”
From CI-994 is a dual modulator of class I HDACs and Wnt/β-catenin signaling for the treatment of Alzheimer's disease (2026) · cites this paper as [7]
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“HDAC inhibitors also demonstrate anti-inflammatory and neuroprotective effects in neurodegenerative models by dampening inflammatory signaling and supporting synaptic and cognitive function (Morrison et al., 2006; Zhou et al., 2018; Kumar et al., 2022).”
From Histone modifications and depression: epigenetic mechanisms, therapeutic targets, and translational outlook (2026) · cites this paper as Kumar et al., 2022
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“while aberrant HDAC3 expression increases neuronal vulnerability (Kumar et al., 2022)”
From Histone modifications and depression: epigenetic mechanisms, therapeutic targets, and translational outlook (2026) · cites this paper as Kumar et al., 2022
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“The ability of HDAC inhibitors to improve behavioral outcomes through anti-inflammatory and neuroplastic mechanisms (Dai et al., 2021; Kumar et al., 2022)”
From Histone modifications and depression: epigenetic mechanisms, therapeutic targets, and translational outlook (2026) · cites this paper as Kumar et al., 2022
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“Growing evidence supports that epigenetic dysregulation through histone deacetylases (HDACs) plays a critical role in synaptic dysfunction and memory loss in Alzheimer’s disease”
From CI-994 is a dual modulator of class I HDACs and Wnt/β-catenin signaling for the treatment of Alzheimer's disease (2026) · cites this paper as [7]
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“HDAC inhibitors can enhance histone acetylation and ameliorate cognitive impairments in various AD models, and HDAC inhibition has been recognized as an attractive therapeutic strategy for AD [4, 5, 7].”
From CI-994 is a dual modulator of class I HDACs and Wnt/β-catenin signaling for the treatment of Alzheimer's disease (2026) · cites this paper as [7]
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Citations
Cites
Regulation of chromatin by histone modifications
Bannister, A. J., & Kouzarides, T. (2011) · Cell Research · doi:10.1038/cr.2011.22 · Cited by 6,012
The tumour suppressor protein VHL targets hypoxia-inducible factors for oxygen-dependent proteolysis
Maxwell, P. H., Wiesener, M. S., Chang, G.-W., Clifford, S. C., Vaux, E. C., Cockman, M. E., Wykoff, C. C., Pugh, C. W., Maher, E. R., & Ratcliffe, P. J. (1999) · Nature · doi:10.1038/20459 · Cited by 5,180
Epidemiology of Parkinson's disease
de Lau, L. M., & Breteler, M. M. (2006) · The Lancet Neurology · doi:10.1016/s1474-4422(06)70471-9 · Cited by 4,110
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
Autophagy and the Integrated Stress Response
Kroemer, G., Mariño, G., & Levine, B. (2010) · Molecular Cell · doi:10.1016/j.molcel.2010.09.023 · Cited by 3,506
Histone deacetylases (HDACs): characterization of the classical HDAC family
RUIJTER, A. J. M. D., GENNIP, A. H. V., CARON, H. N., KEMP, S., & KUILENBURG, A. B. P. V. (2003) · Biochemical Journal · doi:10.1042/bj20021321 · Cited by 3,114
Haberland, M., Montgomery, R. L., & Olson, E. N. (2008) · Nature Reviews Genetics · doi:10.1038/nrg2485 · Cited by 2,600
Erasers of Histone Acetylation: The Histone Deacetylase EnzymesPreprint
Seto, E., & Yoshida, M. (2014) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a018713 · Cited by 2,105
Calorie restriction promotes mammalian cell survival by inducing the SIRT1 deacetylase
Cohen, H. Y., Miller, C., Bitterman, K. J., Wall, N. R., Hekking, B., Kessler, B., Howitz, K. T., Gorospe, M., de Cabo, R., & Sinclair, D. A. (2004) · Science · doi:10.1126/science.1099196 · Cited by 1,924
Histone deacetylases and cancer: causes and therapies
Marks, P. A., Rifkind, R. A., Richon, V. M., Breslow, R., Miller, T., & Kelly, W. K. (2001) · Nature reviews. Cancer · doi:10.1038/35106079 · Cited by 1,866
Research works printed but not linked: 4
- Alberts B.; Molecular biology of the cell Garland science 2008
- Alberts B.; Johnson A.; Lewis J.; Raff M.; Roberts K.; Walter P.; Drosophila and the molecular genetics of pattern formation: Genesis of the body planMolecular Biology of the Cell 2002
- Szegő É.M.; Outeiro T.F.; Kazantsev A.G.; Sirtuins in brain and neurodegenerative disease Introductory Review on Sirtuins in Biology, Aging, and Disease 2018,175-195
- Chang, JK Tolfenamic acid: A potential modifier of tau protein in Alzheimer's disease 2015 (Thesis)
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Mitochondria: It is all about energy
Casanova, A., Wevers, A., Ledesma, S. N., & Pruimboom, L. (2023) · Frontiers in Physiology · doi:10.3389/fphys.2023.1114231 · Cited by 350
Targeting histone deacetylases for cancer therapy: Trends and challenges
Liang, T., Wang, F., Elhassan, R. M., Cheng, Y., Tang, X., Chen, W., Fang, H., & Hou, X. (2023) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2023.02.007 · Cited by 222
The interaction between ageing and Alzheimer's disease: insights from the hallmarks of ageing
Liu, Y., Tan, Y., Zhang, Z., Yi, M., Zhu, L., & Peng, W. (2024) · Translational Neurodegeneration · doi:10.1186/s40035-024-00397-x · Cited by 156
Cao, Q., Shen, M., Li, R., Liu, Y., Zeng, Z., Zhou, J., Niu, D., Zhang, Q., Wang, R., Yao, J., et al. (2025) · Journal of Neuroinflammation · doi:10.1186/s12974-025-03454-y · Cited by 138
Huang, J., Wang, X., Li, N., Fan, W., Li, X., Qian, Z., Liu, J., Li, W., Zhang, Z., Liu, X., et al. (2024) · Advanced Science · doi:10.1002/advs.202308031 · Cited by 102
Metadata
- Authors
- Kumar, V., Kundu, S., Singh, A., & Singh, S.
- Affiliations
- Indo Soviet Friendship College of Pharmacy (IN)
- Corresponding author
- Singh, Shamsher
- Venue
- Current Neuropharmacology
- Publisher
- Bentham Science Publishers Ltd.
- Published
- 2022-01
- Volume
- 20
- Issue
- 1
- Pages
- 158-178
- ISSN
- 1570-159X (ISSN-L)
- PMC
- PMC9199543
- OpenAlex
- W3174079095
- Cited by
- 210
- References
- 185
- Citations by year
- 2026: 46 · 2025: 60 · 2024: 54 · 2023: 35 · 2022: 14
- FWCI
- 2.73
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- cc-by-nc
- Locations
- Current Neuropharmacology (publishedVersion)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Histone Deacetylase Inhibitors Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Keywords
- histone deacetylase, histone deacetylase inhibitors, neurodegenerative diseases, class I HDACs, class II HDACs, sirtuins, SIRT1, SIRT2, SIRT6, neuroprotection, Alzheimer's disease, Parkinson's disease, Huntington's disease, oxidative stress, neuroinflammation, mitochondrial dysfunction, excitotoxicity, brain-derived neurotrophic factor, tau phosphorylation, glial fibrillary acidic protein
- MeSH terms
- Neuroinflammatory Diseases, Brain, Histone Deacetylases, Humans, Neurodegenerative Diseases, Sirtuins
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