Human neuronal cells: epigenetic aspects

Abstract

Histone acetyltransferases (HATs) and histone deacetylases (HDACs) promote histone posttranslational modifications, which lead to an epigenetic alteration in gene expression. Aberrant regulation of HATs and HDACs in neuronal cells results in pathological consequences such as neurodegeneration. Alzheimer's disease is the most common neurodegenerative disease of the brain, which has devastating effects on patients and loved ones. The use of pan-HDAC inhibitors has shown great therapeutic promise in ameliorating neurodegenerative ailments. Recent evidence has emerged suggesting that certain deacetylases mediate neurotoxicity, whereas others provide neuroprotection. Therefore, the inhibition of certain isoforms to alleviate neurodegenerative manifestations has now become the focus of studies. In this review, we aimed to discuss and summarize some of the most recent and promising findings of HAT and HDAC functions in neurodegenerative diseases.

RETRACTED: Inhibition of HDAC4 Attenuated JNK/c-Jun-Dependent Neuronal Apoptosis and Early Brain Injury Following Subarachnoid Hemorrhage by Transcriptionally Suppressing MKK7

“…The inhibition of histone deacetylase (HDAC) has been demonstrated independently to prevent neuronal apoptosis induced by oxidative stress or DNA damage. Furthermore, several nervous diseases, including SAH, Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), and ischemia, were ameliorated with obvious decreases in apoptosis after the administration of HDAC inhibitors (Kukucka et al, 2013; Didonna and Opal, 2015; Shao et al, 2016), which suggests that HDACs play crucial roles in the apoptotic neurons suffering from extreme stimuli. However, the related mechanisms remain largely elusive.…”

Intravitreal Injection of Liposomes Loaded with a Histone Deacetylase Inhibitor Promotes Retinal Ganglion Cell Survival in a Mouse Model of Optic Nerve Crush

“…A balanced histone acetyltransferase (HAT) and histone deacetylase (HDAC) interplay is vital for neuronal cell functionality, thereby coordinating gene expression in a healthy manner. During a neurodegenerative state, this balance is altered, and HDAC activity overrides HAT activity [28,29]. HDACs and their inhibitors have emerged as promising targets for regulating neurodegenerative disorders.…”

HDACi: The Columbus’ Egg in Improving Cancer Treatment and Reducing Neurotoxicity?

“…More in detail, it could act as a nucleus–cytoplasm shuttle [ 36 ], and that can operate as a neurodegeneration promoter by inducing inflammation and neurodegenerative processes [ 22 ]. HDAC3 overexpression is linked to higher rates of cortex and cerebellum neuronal death, apoptosis and toxicity [ 41 ]. Moreover, recent studies indicate that HDAC3 expression promotes neurodegenerative diseases such as PD, AD and HD.…”

“…To summarize, HDAC3 can have a strong neurotoxic action on adult neurons in the brain, leading to neurodegenerative diseases, such as HD. For these reasons, it is currently an attractive target to inhibit for possible future studies on neurodegenerative diseases [ 41 ], such as for AD treatment. Nevertheless, it could be of great interest to discern its epigenetic regulator role in neurogenesis and gliogenesis.…”