Measuring histone deacetylase inhibition in the brain
Open accessAbstract
Histone deacetylases (HDACs) represent a family of enzymes that are targets for epigenetic modulation of genomic activity and may be beneficial in the treatment of many diseases, including cancer and central nervous system disorders. In animal models, HDAC inhibitors have neuroprotective, antiepileptogenic, and antidepressant effects. Assaying HDAC activity provides a robust method for identifying HDAC inhibitors and for assessing their effects under various physiological conditions or after pathological insults. In this unit, a simple and sensitive assay for measuring HDAC activity is described. HDAC activity in tissue lysates can be assessed fluorometrically using a Boc‐Lys(Ac) HDAC activity kit. HDACs catalyze the deacetylation of the substrate Boc‐Lys(Ac)‐AMC. Addition of a trypsin‐containing developer converts the deacetylated product to a quantifiable fluorophore that can be used both as a screening method to identify putative HDAC inhibitors and to assess the effects of these inhibitors on tissue and animal epigenetic‐modulated phenotypes. © 2018 by John Wiley & Sons, Inc.
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Inhibition of histone deacetylases has been considered the main effector mechanism triggered by short-chain fatty acids in their effects on microglia.
“inhibition of HDACs, which results in epigenetically regulated gene expression, has been considered the main effector mechanism triggered by SCFAs (113).”
From The Role of Short-Chain Fatty Acids From Gut Microbiota in Gut-Brain Communication (2020) · cites this paper as [113]
The Commentary (Background Information; page unavailable) says sodium butyrate inhibits HDACs in the brain and explains how HDAC inhibition can regulate gene transcription. The paper does not establish that HDAC inhibition is the main mechanism of short-chain fatty acids generally, or address that mechanism in microglia. (LLM, conf=0.86)
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Cited by
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The Role of Short-Chain Fatty Acids From Gut Microbiota in Gut-Brain Communication
Silva, Y. P., Bernardi, A., & Frozza, R. L. (2020) · Frontiers in Endocrinology · doi:10.3389/fendo.2020.00025 · Cited by 3,043 · see citing works
“Although the precise signaling involved in the effects of SCFAs on microglia remain unveiled, inhibition of HDACs, which results in epigenetically regulated gene expression, has been considered the main effector mechanism triggered by SCFAs (113).”
BackgroundMicrobial-derived metabolites as a risk factor of age-related cognitive decline and dementia
Connell, E., Le Gall, G., Pontifex, M. G., Sami, S., Cryan, J. F., Clarke, G., Müller, M., & Vauzour, D. (2022) · Molecular Neurodegeneration · doi:10.1186/s13024-022-00548-6 · Cited by 208 · see citing works
Chidambaram, S. B., Essa, M. M., Rathipriya, A. G., Bishir, M., Ray, B., Mahalakshmi, A. M., Tousif, A. H., Sakharkar, M. K., Kashyap, R. S., Friedland, R. P., et al. (2022) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2021.107988 · Cited by 204 · see citing works
- Authors
- Reddy, D. S., Wu, X., Golub, V. M., Dashwood, W. M., & Dashwood, R. H.
- Affiliations
- Texas A&M Health Science Center (US)
- Texas A&M University (US)
- Corresponding author
- Reddy, Doodipala Samba
- Venue
- Current Protocols in Pharmacology
- Publisher
- Wiley
- Published
- 2018-06
- Volume
- 81
- Issue
- 1
- Pages
- e41-e41
- ISSN
- 1934-8282 (ISSN-L)
- 1934-8290
- PMC
- PMC6019607
- OpenAlex
- W2806123424
- Cited by
- 33
- References
- 4
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 2 · 2023: 5 · 2022: 6 · 2021: 7 · 2020: 5 · 2019: 2
- FWCI
- 1.25
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Current Protocols in Pharmacology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Cancer Institute (R01CA122959)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Histone Deacetylase Inhibitors Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Enzyme function and inhibition
- Keywords
- histone deacetylase inhibition, fluorometric assay, epigenetic modulation, histone deacetylase inhibitors, neuroprotection, antiepileptogenic effects, antidepressant effects, drug screening
- MeSH terms
- Brain Injuries, Traumatic, Animals, Brain, Histone Deacetylases, Nuclear Proteins, Mice, Histone Deacetylase Inhibitors
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