Molecular targets of histone deacetylase inhibitors in neurodegeneration and neuroprotection

Abstract

BackgroundNeurodegenerative diseases show various phenotypes of molecular and cellular malfunction including mitochondrial dysfunction and neuroinflammation. These molecular dynamics are based on the epigenetic regulation of the gene expression in the cells, which are vulnerable to progressive neurodegeneration. Histone deacetylases (HDAC) are the enzymes that remove acetyl group from histones or non-histone proteins for the transcriptional control. Thus, HDAC inhibitors (HDACi) have been proposed as prominent drugs for neurodegenerative diseases.ObjectivesIn this study, we explain the molecular targets of the HDACi in the processes of neurodegeneration and neuroprotection.ResultsTreatment with HDACi altered the expression of specific genes that are associated with mitochondrial bioenergetics and neuroinflammation.ConclusionsMitochondrial bioenergetics- and neuroinflammation-related molecular targets of HDACi may be the key to the use of HDACi therapy for neurodegenerative diseases.Purpose of reviewWe aimed to discover molecular targets of HDACi in progressive neurodegeneration and to use these targets in potential therapeutics to induce neuroprotection.Recent findingsHDACi reverse cellular pathology in a mechanism involving mitochondrial bioenergetics and neuroinflammation, and the result is alleviation of pathologic phenotypes of neurodegenerative diseases.