HDAC4 in ischemic stroke: mechanisms and therapeutic potential

Kong, Qingsheng; Hao, Yongnan; Li, Xin; Wang, Xin; Ji, Bingyuan; Wu, Yili

doi:10.1186/s13148-018-0549-1

Cited by 35 publications

(31 citation statements)

References 92 publications

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“…Moreover, TMP21could affect AD pathogenesis via altering epigenetic regulation. For example, PI3K/Akt pathway is involved in regulating the function of histone deacetylase 4 (HDAC4), while HDAC4 plays a pivotal role in various neurological diseases including AD [40–42]. These evidence suggests that dysregulation of TMP21 might play a complex role in the pathogenesis of AD in addition to regulating protein trafficking and γ-secretase activity.…”

Section: Discussionmentioning

confidence: 99%

Regulation of global gene expression in brain by TMP21

Zhang

Cai

et al. 2019

Mol Brain

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TMP21, a type I transmembrane protein of thep24 protein family, mediates protein trafficking and maturation. Dysregulation of TMP21 is implicated in the pathogenesis of Alzheimer’s disease (AD). However, underlying mechanisms remain elusive. To reveal the function of TMP21 in the brain and the pathogenic role of TMP21 in the brain of AD, the global gene expression was profiled in the brain of TMP21 knockdown mice. We found that 8196 and 8195 genes are significantly altered in the hippocampus and cortex, respectively. The genes are involved in a number of brain function-related pathways, including glutamatergic synapse pathway, serotonergic synapse pathway, synaptic vesicle pathway, and long-term depression pathway. Moreover, the network analysis suggests that the TMP21 may contribute to the pathogenesis of AD by regulatingPI3K/Akt/GSK3β signalling pathway. Our study provides an insight into the physiological function of TMP21 in the brain and pathological role of TMP21 in AD.

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Section: Discussionmentioning

confidence: 99%

Regulation of global gene expression in brain by TMP21

Zhang

Cai

et al. 2019

Mol Brain

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“…In ischemic stroke models, HDAC4 expression is reduced, while HDAC4 may reduce neuronal apoptosis by decreasing high-mobility group box 1 (hMGB1) protein expression and promote angiogenesis and nerve regeneration through the release of VEGF signal of hypoxia-inducible factor-1 [ 35 – 37 ]. HDAC4's interactive partners such as MEF2, ATF4, and NF- κ B may also mediate the roles of attenuation of neuronal apoptosis and promotion of angiogenesis and neurogenesis of ischemic stroke [ 38 ].…”

Section: Hdacs In Cerebral Ischemiamentioning

confidence: 99%

Updating a Strategy for Histone Deacetylases and Its Inhibitors in the Potential Treatment of Cerebral Ischemic Stroke

Wang

Chen

et al. 2020

Disease Markers

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Background. Cerebral ischemic stroke is one of the severe diseases with a pathological condition that leads to nerve cell dysfunction with seldom available therapy options. Currently, there are few proven effective treatments available for improving cerebral ischemic stroke outcome. However, recently, there is increasing evidence that inhibition of histone deacetylase (HDAC) activity exerts a strong protective effect in in vivo and vitro models of ischemic stroke. Review Summary. HDAC is a posttranslational modification that is negatively regulated by histone acetyltransferase (HATS) and histone deacetylase. Based on function and DNA sequence similarity, histone deacetylases (HDACs) are organized into four different subclasses (I-IV). Modifications of histones play a crucial role in cerebral ischemic affair development after translation by modulating disrupted acetylation homeostasis. HDAC inhibitors (HDACi) mainly exert neuroprotective effects by enhancing histone and nonhistone acetylation levels and enhancing gene expression and protein modification functions. This article reviews HDAC and its inhibitors, hoping to find meaningful therapeutic targets. Conclusions. HDAC may be a new biological target for cerebral ischemic stroke. Future drug development targeting HDAC may make it a potentially effective anticerebral ischemic stroke drug.

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“…Recently, a relationship between HDAC4 and IS was highlighted. Kong et al described that HDAC4 was reduced in neuronal cells isolated from MCAO rat model and subjected to oxygen-glucose deprivation (OGD) [68]. Low levels of HDAC4 were associated with alterations in cell proliferation and angiogenesis [69] and with loss of integrity of the blood-brain barrier (BBB) [70].…”

Section: Histone Modifications In Ismentioning

confidence: 99%

Pathogenesis of Ischemic Stroke: Role of Epigenetic Mechanisms

Stanzione

Cotugno

Bianchi

et al. 2020

Genes

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Epigenetics is the branch of molecular biology that studies modifications able to change gene expression without altering the DNA sequence. Epigenetic modulations include DNA methylation, histone modifications, and noncoding RNAs. These gene modifications are heritable and modifiable and can be triggered by lifestyle and nutritional factors. In recent years, epigenetic changes have been associated with the pathogenesis of several diseases such as diabetes, obesity, renal pathology, and different types of cancer. They have also been related with the pathogenesis of cardiovascular diseases including ischemic stroke. Importantly, since epigenetic modifications are reversible processes they could assist with the development of new therapeutic approaches for the treatment of human diseases. In the present review article, we aim to collect the most recent evidence concerning the impact of epigenetic modifications on the pathogenesis of ischemic stroke in both animal models and humans.

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HDAC4 in ischemic stroke: mechanisms and therapeutic potential

Cited by 35 publications

References 92 publications

Regulation of global gene expression in brain by TMP21

Regulation of global gene expression in brain by TMP21

Updating a Strategy for Histone Deacetylases and Its Inhibitors in the Potential Treatment of Cerebral Ischemic Stroke

Pathogenesis of Ischemic Stroke: Role of Epigenetic Mechanisms

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