Development of a novel histone deacetylase inhibitor unveils the role of HDAC11 in alleviating depression by inhibition of microglial activation

Baek, Soo Yeon; Lee, J. Y.; Kim, Taegwan; Lee, Hye-Lim; Choi, Hoon-Seong; Park, Hahnbeom; Koh, Minseob; Kim, Eunha; Jung, Michael E.; Iliopoulos, Dimitrios; Lee, Jeong-Yeon; Kim, Jonghoon; Lee, Sanghee

doi:10.1016/j.biopha.2023.115312

Cited by 8 publications

(3 citation statements)

References 35 publications

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“…In addition, mice with conditional knockout of the HDAC9 gene from forebrain neurons reversed depressive disorders caused by chronic restraint stress [ 106 ]. In addition, HDAC11 is also involved in regulating the homeostasis of autophagy and nitric oxide in the microglia of depression-like mice [ 107 ].…”

Section: Role Of Chromatin Modifiers In Human Diseasesmentioning

confidence: 99%

Chromatin modifiers in human disease: from functional roles to regulatory mechanisms

Nie,

Song,

Huang

et al. 2024

Mol Biomed

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The field of transcriptional regulation has revealed the vital role of chromatin modifiers in human diseases from the beginning of functional exploration to the process of participating in many types of disease regulatory mechanisms. Chromatin modifiers are a class of enzymes that can catalyze the chemical conversion of pyrimidine residues or amino acid residues, including histone modifiers, DNA methyltransferases, and chromatin remodeling complexes. Chromatin modifiers assist in the formation of transcriptional regulatory circuits between transcription factors, enhancers, and promoters by regulating chromatin accessibility and the ability of transcription factors to acquire DNA. This is achieved by recruiting associated proteins and RNA polymerases. They modify the physical contact between cis-regulatory factor elements, transcription factors, and chromatin DNA to influence transcriptional regulatory processes. Then, abnormal chromatin perturbations can impair the homeostasis of organs, tissues, and cells, leading to diseases. The review offers a comprehensive elucidation on the function and regulatory mechanism of chromatin modifiers, thereby highlighting their indispensability in the development of diseases. Furthermore, this underscores the potential of chromatin modifiers as biomarkers, which may enable early disease diagnosis. With the aid of this paper, a deeper understanding of the role of chromatin modifiers in the pathogenesis of diseases can be gained, which could help in devising effective diagnostic and therapeutic interventions.

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Section: Role Of Chromatin Modifiers In Human Diseasesmentioning

confidence: 99%

Chromatin modifiers in human disease: from functional roles to regulatory mechanisms

Nie,

Song,

Huang

et al. 2024

Mol Biomed

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show abstract

“…This study identified a set of autophagy-related genes and inflammatory genes separately as direct targets activated by acetylation of H3K9, however, whether autophagy is causally related to neuroinflammation regulation by histone acetylation needs to be further examined. More recently, a study discovered a new HDAC11 specific inhibitor named compound five, “5” ( 156 ). 5 inhibits deacetylase function of HDAC11 and attenuate microglia-medicated neuroinflammation through induction of autophagy and reduction of reactive nitrogen species.…”

Section: Autophagy and Neuroinflammation In Neurodegenerative Diseasesmentioning

confidence: 99%

Epigenetic regulation of autophagy in neuroinflammation and synaptic plasticity

Bai,

Keyser,

Zhang

et al. 2024

Front. Immunol.

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Autophagy is a conserved cellular mechanism that enables the degradation and recycling of cellular organelles and proteins via the lysosomal pathway. In neurodevelopment and maintenance of neuronal homeostasis, autophagy is required to regulate presynaptic functions, synapse remodeling, and synaptic plasticity. Deficiency of autophagy has been shown to underlie the synaptic and behavioral deficits of many neurological diseases such as autism, psychiatric diseases, and neurodegenerative disorders. Recent evidence reveals that dysregulated autophagy plays an important role in the initiation and progression of neuroinflammation, a common pathological feature in many neurological disorders leading to defective synaptic morphology and plasticity. In this review, we will discuss the regulation of autophagy and its effects on synapses and neuroinflammation, with emphasis on how autophagy is regulated by epigenetic mechanisms under healthy and diseased conditions.

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“…Similar phenomena are also found in the autopsy of anxiety patients and animals ( Sah et al, 2019 ; Peng et al, 2021 ). Moreover, several studies show that histone deacetylase inhibitor (HDACi) can ameliorate anxiety- and depression-like behavior in patients and rodents ( Sah et al, 2019 ; Peng et al, 2021 ; Choi, 2022 ; Baek et al, 2023 ). Taken together, these findings suggest that is closely involved in the pathophysiology of anxiety and depression is closely related to histone acetylation.…”

Section: Introductionmentioning

confidence: 99%

Trichostatin A relieves anxiety-and depression-like symptoms in APP/PS1 mice

Su,

Ren,

Liu

et al. 2024

Front. Pharmacol.

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Background:Cognitive deficits and behavioral disorders such as anxiety and depression are common manifestations of Alzheimer’s disease (AD). Our previous work demonstrated that Trichostatin A (TSA) could alleviate neuroinflammatory plaques and improve cognitive disorders. AD, anxiety, and depression are all associated with microglial inflammation. However, whether TSA could attenuate anxiety- and depression-like behaviors in APP/PS1 mice through anti-inflammatory signaling is still unclearly.Methods:In the present study, all mice were subjected to the open field, elevated plus maze, and forced swim tests to assess anxiety- and depression-related behaviors after TSA administration. To understand the possible mechanisms underlying the behavioral effects observed, CST7 was measured in the hippocampus of mice and LPS-treated BV2 microglia.Results:The results of this study indicated that TSA administration relieved the behaviors of depression and anxiety in APP/PS1 mice, and decreased CST7 levels in the hippocampus of APP/PS1 mice and LPS-induced BV2 cells.Conclusion:Overall, these findings support the idea that TSA might be beneficial for reducing neurobehavioral disorders in AD and this could be due to suppression of CST7-related microglial inflammation.

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Development of a novel histone deacetylase inhibitor unveils the role of HDAC11 in alleviating depression by inhibition of microglial activation

Cited by 8 publications

References 35 publications

Chromatin modifiers in human disease: from functional roles to regulatory mechanisms

Chromatin modifiers in human disease: from functional roles to regulatory mechanisms

Epigenetic regulation of autophagy in neuroinflammation and synaptic plasticity

Trichostatin A relieves anxiety-and depression-like symptoms in APP/PS1 mice

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