Histone Deacetylase (HDAC) Inhibitors: Research and Therapeutic Applications in Cancer and Neurodegenerative...

Cancer and neurodegenerative disorders remain major public health challenges worldwide. Increasing incidence across age groups, together with persistently high mortality in many settings, contributes to substantial socioeconomic burdens on individuals, families, and healthcare systems. Histone Deacetylases (HDACs) are enzymes that remove acetyl groups from lysine residues on histone tails. As a key post-translational modification, histone deacetylation modulates chromatin organization and gene transcription. In many contexts, HDACmediated deacetylation is associated with increased chromatin compaction, which may limit transcription-factor accessibility and reduce transcriptional output. Beyond chromatin regulation, HDACs have been implicated in cell-cycle progression, apoptosis, inflammation, immune responses, redox homeostasis, and neuronal development. Given their involvement in disease mechanisms, Histone Deacetylase Inhibitors (HDACis) have attracted attention as potential epigenetic therapeutics with pleiotropic effects. By counteracting aberrant deacetylation, HDACis may help restore acetylation-dependent transcriptional programs and reactivate genes implicated in disease. They may also affect dysregulated signaling pathways and have been reported to exhibit antiproliferative, anti-inflammatory, neuroprotective, and anticancer effects. Accumulating preclinical and emerging clinical evidence suggests that HDACis are being evaluated for therapeutic activity in a range of malignant and neurodegenerative diseases. This review summarizes recent advances in HDACis, with emphasis on structural classification, key chemical features, molecular mechanisms, and clinical translation in oncology and neurodegeneration. By integrating these aspects, the article aims to provide a conceptual reference for targeted drug discovery and rational combination strategies for these challenging conditions.