Emerging Neuroprotective Strategies: Unraveling the Potential of HDAC Inhibitors in Traumatic Brain Injury Management

作者：Lisha Ye, Wenfeng Li, Xiaoyan Tang, Ting Xu, Guohua Wang · 发表于：Current Neuropharmacology · 年份：2024 · DOI：10.2174/1570159x22666240128002056 · 被引用次数：15 · 研究领域：Histone Deacetylase Inhibitors Research、Protein Degradation and Inhibitors、Signaling Pathways in Disease

Traumatic brain injury (TBI) is a significant global health problem, leading to high rates of mortality and disability. It occurs when an external force damages the brain, causing immediate harm and triggering further pathological processes that exacerbate the condition. Despite its widespread impact, the underlying mechanisms of TBI remain poorly understood, and there are no specific pharmacological treatments available. This creates an urgent need for new, effective neuroprotective drugs and strategies tailored to the diverse needs of TBI patients. In the realm of gene expression regulation, chromatin acetylation plays a pivotal role. This process is controlled by two classes of enzymes: histone acetyltransferase (HAT) and histone deacetylase (HDAC). These enzymes modify lysine residues on histone proteins, thereby determining the acetylation status of chromatin. HDACs, in particular, are involved in the epigenetic regulation of gene expression in TBI. Recent research has highlighted the potential of HDAC inhibitors (HDACIs) as promising neuroprotective agents. These compounds have shown encouraging results in animal models of various neurodegenerative diseases. HDACIs offer multiple avenues for TBI management: they mitigate the neuroinflammatory response, alleviate oxidative stress, inhibit neuronal apoptosis, and promote neurogenesis and axonal regeneration. Additionally, they reduce glial activation, which is associated with TBI-induced neuroinflammation. This review aim...