The Two Faces of HDAC3: Neuroinflammation in Disease and Neuroprotection in Recovery
Creators: name: Rosete, Cal
name: Ciernia, Annie Vogel
Publisher: name: Taylor & Francis
Year: 2024
Subjects: subject: Biochemistry
subject: Medicine
subject: Cell Biology
subject: Genetics
subject: FOS: Biological sciences
subject: Molecular Biology
subject: Neuroscience
subject: Pharmacology
subject: Immunology
subject: FOS: Clinical medicine
subject: Biological Sciences not elsewhere classified
subject: Mental Health

description: Histone deacetylase 3 (HDAC3) is a critical regulator of gene expression, influencing a variety of cellular processes in the central nervous system. As such, dysfunction of this enzyme may serve as a key driver in the pathophysiology of various neuropsychiatric disorders and neurodegenerative diseases. HDAC3 plays a crucial role in regulating neuroinflammation, and is now widely recognized as a major contributor to neurological conditions, as well as in promoting neuroprotective recovery following brain injury, hemorrhage and stroke. Emerging evidence suggests that pharmacological inhibition of HDAC3 can mitigate behavioral and neuroimmune deficits in various brain diseases and disorders, offering a promising therapeutic strategy. Understanding HDAC3 in the healthy brain lays the necessary foundation to define and resolve its dysfunction in a disease state. This review explores the mechanisms of HDAC3 in various cell types and its involvement in disease pathology, emphasizing the potential of HDAC3 inhibition to address neuroimmune, gene expression and behavioral deficits in a range of neurodegenerative and neuropsychiatric conditions. Histone deacetylase 3 (HDAC3) is an essential enzyme that helps regulate gene expression in the brain, influencing a variety of processes critical for brain health. Dysfunction of this enzyme may contribute to various brain disorders and diseases, including Alzheimer's disease, Parkinson's disease, Huntington's disease, spinal cord injury, stroke and major depressive disorder. HDAC3 is involved in the brain's response to injury and disease through dual roles in neuroinflammation and neuroprotection. Recent evidence suggests that inhibiting HDAC3 can mitigate detrimental immune processes in the brain, making it a promising target for new therapies. By understanding HDAC3 in the healthy brain, we can better identify how its dysfunction contributes to disease and how its inhibition may aid in recovery. This review explores the mechanisms of HDAC3 in various brain cell types and explores its potential as a therapeutic target for treating neurodegenerative and neuropsychiatric conditions. HDAC3 modulates cell type specific gene expression through histone and non-histone transcriptional regulators to control both neuroinflammation and neuroprotection. Within the brain, HDAC3 promotes neuroinflammation through the repression of inflammation-resolving pathways via histone deacetylation. HDAC3 promotes neuroprotective mechanisms through its interaction with non-histone proteins, such as transcription factors and signalling pathways that promote cell survival and repair HDAC3 inhibition reduces astrocyte reactivity and pro-inflammatory microglia and macrophages phenotypes, while promoting myelination, oligodendrocyte maturation and neural plasticity Inhibition of HDAC3 ameliorates various neuroinflammatory symptoms in animal models of disease states, including neurodegenerative disease, spinal cord injury and neuropsychiatric symptoms such as stress, anxiety and depression