Title:Emerging Neuroprotective Strategies: Unraveling the Potential of HDAC Inhibitors in Traumatic Brain Injury Management
Volume: 22
Issue: 14
Author(s): Lisha Ye, Wenfeng Li, Xiaoyan Tang, Ting Xu and Guohua Wang*
Affiliation:
- Department of Neurophysiology and Neuropharmacology, Institute of Special Environmental Medicine and
Co-Innovation Center of Neuroregeneration, Nantong University, 9 Seyuan Road, Chongchuan District, Nantong,
Jiangsu 226019, China
Keywords:
Traumatic brain injury, neuroprotective drugs, HDAC inhibitors, neuroinflammation, oxidative stress, neuronal apoptosis, axonal regeneration, glial activation.
Abstract: 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
aims to provide a comprehensive overview of the roles and mechanisms of HDACs in TBI and to
evaluate the therapeutic potential of HDACIs. By summarizing current knowledge and emphasizing
the neuroregenerative capabilities of HDACIs, this review seeks to advance TBI management and contribute
to the development of targeted treatments.
