Tubacin, HDAC6 inhibitor, protects dopaminergic neurons in MPTP mice

Abstract

Parkinson’s disease (PD) is caused by selective vulnerability of dopaminergic neurons in substantial nigra (SN). As an external cause, MPTP [1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine] targets specifically those dopaminergic neurons involved in PD pathology, and has been commonly used for PD model. Histone deacetylase (HDAC) has critical function to unwrap DNA from histone by deacetylation and regulates specific function to unwrap DNA from histone by deacetylation and regulates specific gene expression for cell fate determination. In addition, it also targets non-histone proteins and regulates various cellular functions. As administration of HDAC inhibitors has been reported as potential therapeutic target in several neurodegenerative diseases, we hypothesized that inhibition of HDAC6 (class IIb HDAC) with tubacin induces neuroprotection in MPTP PD mouse model. We found that tubacin increased the number of tyrosine hydroxylase (TH)-positive dopaminergic neurons in the SN regions and reduced the number of activated microglia. In addition, tubacin significantly improved motor balance in MPTP mice. These results suggest that tubacin could be used to study neuroprotection mechanism and future therapeutic application for PD.