Journal
NEUROCHEMISTRY INTERNATIONAL
Volume 150, Issue -, Pages -Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuint.2021.105182
Keywords
Histone deacetylases; Neuroinflammation; Histone deacetylases inhibitor
Categories
Funding
- National Natural Science Foundation of China [82173789, 81573402, 81773700]
- Zhejiang Provincial Natural Science Foundation of China [Y19H090117, YY19H310010, LY16H310001]
- Health Bureau of Zhejiang Province [2018RC036]
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Neuroinflammation plays a key role in various neurological diseases, with inhibition of neuroinflammation shown to reduce disease severity. Epigenetics regulates gene expression through mechanisms such as DNA methylation and histone modification, with HDACs being important enzymes in this process. HDACs are involved in regulating immunity and inflammation, making HDAC inhibitors a new focus in anti-inflammatory drug research.
Neuroinflammation is a key factor of the pathology of various neurological diseases (brain injury, depression, neurodegenerative diseases). It is a complex and orderly process that relies on various types of glial cells and peripheral immune cells. Inhibition of neuroinflammation can reduce the severity of neurological diseases. The initiation, progression, and termination of inflammation require gene activation, epigenetic modification, transcriptional translation, and post-translational regulation, all of which are tightly regulated by different enzymes. Epigenetics refers to the regulation of epigenetic gene expression by epigenetic changes (DNA methylation, histone modification, and non-coding RNAs such as miRNA) that are not dependent on changes in gene sequence and are heritable. Histone deacetylases (HDACs) are a group of important enzymes that regulate epigenetics. They can remove the acetyl group on the lysine epsilon-amino group of the target protein, thereby affecting gene transcription or altering protein activity. HDACs are involved in the regulation of immunity and inflammation. HDAC inhibitor (HDACi) has also become a new hotspot in the research of anti-inflammatory drugs. Therefore, the aim of the current review is to discuss and summarize the role and mechanism of different HDACs in neuroinflammation and the corresponding role of HDACi in neurological diseases, and to providing new ideas for future research on neuroinflammation-related diseases and drug development.
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