Abstract
Background
Neurodegenerative diseases show various phenotypes of molecular and cellular malfunction including mitochondrial dysfunction and neuroinflammation. These molecular dynamics are based on the epigenetic regulation of the gene expression in the cells, which are vulnerable to progressive neurodegeneration. Histone deacetylases (HDAC) are the enzymes that remove acetyl group from histones or non-histone proteins for the transcriptional control. Thus, HDAC inhibitors (HDACi) have been proposed as prominent drugs for neurodegenerative diseases.
Objectives
In this study, we explain the molecular targets of the HDACi in the processes of neurodegeneration and neuroprotection.
Results
Treatment with HDACi altered the expression of specific genes that are associated with mitochondrial bioenergetics and neuroinflammation.
Conclusions
Mitochondrial bioenergetics- and neuroinflammation-related molecular targets of HDACi may be the key to the use of HDACi therapy for neurodegenerative diseases.
Purpose of review
We aimed to discover molecular targets of HDACi in progressive neurodegeneration and to use these targets in potential therapeutics to induce neuroprotection.
Recent findings
HDACi reverse cellular pathology in a mechanism involving mitochondrial bioenergetics and neuroinflammation, and the result is alleviation of pathologic phenotypes of neurodegenerative diseases.
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Data availability
All data are available in the original article.
Abbreviations
- HDAC:
-
Histone deacetylase
- HDACi:
-
Histone deacetylase inhibitor
- AD:
-
Alzheimer’s disease
- PD:
-
Parkinson’s disease
- HD:
-
Huntington’s disease
- ALS:
-
Amyotrophic lateral sclerosis
- ROS:
-
Reactive oxygen species
- ATP:
-
Adenosine triphosphate
- OXPHOS:
-
Oxidative phosphorylation
- HAT:
-
Histone acetyltransferase
- NAD+ :
-
Nicotinamide adenine dinucleotide
- ZBM:
-
Zinc-binding moiety
- SAHA:
-
Suberoylanilide hydroxamic acid (vorinostat)
- SB:
-
Sodium butyrate
- BBB:
-
Blood–brain barrier
- GWAS:
-
Genome-wide association study
- VPA:
-
Valproic acid
- CFC:
-
Contextual fear conditioning
- TSA:
-
Trichostatin A
- CNS:
-
Central nervous system
- ChIP-seq:
-
Chromatin immunoprecipitation-sequencing
- 6-OHDA:
-
6-Hydroxydopamine
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Acknowledgements
This work was supported by the National Research Foundation of Korea (NRF) funded by Korea Ministry of Science and ICT (MSIT), and Institute of Information & Communications Technology Planning & Evaluation (IITP) (NRF-2022R1A2C1011996, NRF-2022K1A3A1A20015190, RS-2023-00302751, 2020-0-01343).
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YP and HS designed the study. YP, SY, SYH, and HS wrote the paper. All authors have read and approved the final manuscript.
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All authors declare that they have no conflicts of interest. Yeongwon Park declares that she has no conflicts of interest. Shangfei Yu declares that she has no conflicts of interest. Seung Yong Hwang declares that he has no conflicts of interest. Hyemyung Seo declares that she has no conflicts of interest.
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Park, Y., Yu, S., Hwang, S. et al. Molecular targets of histone deacetylase inhibitors in neurodegeneration and neuroprotection. Mol. Cell. Toxicol. (2024). https://doi.org/10.1007/s13273-024-00441-x
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DOI: https://doi.org/10.1007/s13273-024-00441-x