The Function of HDAC6 Mediated Prx2 Acetylation in Neuronal Apoptosis Related Alzheimer's disease

Abstract

The role of histone deacetylases 6 (HDAC6) in the treatment of neurodegenerative diseases, including Alzheimer's disease (AD), has been extensively studied. Inhibiting and reducing HDAC6 expression has been found to improve cognitive function in AD mice models. Peroxidase 2 (Prx2), an antioxidant enzyme and substrate of HDAC6, is known to provide protection against oxidative stress-induced cell death. This study aims to investigate the effect of the HDAC6-Prx2 signaling pathway on cognitive function and neuronal apoptosis in AD models both in vitro and in vivo. Our results show that the HDAC6-Prx2 association can reduce neuronal apoptosis in the hippocampus and thereby improve learning and memory function in AD mice models. Reduction in HDAC6 levels enhances the acetylated level of Prx2, leading to an increase in its antioxidant capacity. Additionally, acetylated Prx2-mediated reactive oxygen species (ROS) generation is closely linked to neuronal apoptosis. By increasing the acetylation levels of Prx2, ROS levels can be reduced, thereby reducing neuronal apoptosis due to HDAC6 inhibition. Our findings suggest that reduced acetylation levels of Prx2, regulated by HDAC6, may contribute to the neuronal apoptosis and cognitive impairments observed in AD. Therefore, reducing HDAC6 and enhancing the Prx2 acetylation level may be an effective treatment strategy for ameliorating cognitive function in AD mice models.