hdac6 inhibitor blocks amyloid beta-induced impairment of mitochondrial transport in hippocampal neuronshdac6抑制剂阻断淀粉样beta-induced损伤海马神经元线粒体运输.pdfVIP

HDAC6 Inhibitor Blocks Amyloid Beta-Induced Impairment of Mitochondrial Transport in Hippocampal Neurons 1. 1. 1 1 2,3 2,3 Chaeyoung Kim , Heesun Choi , Eun Sun Jung , Wonik Lee , Soojung Oh , Noo Li Jeon , Inhee Mook-Jung1* 1 Department of Biochemistry and Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea, 2 School of Mechanical and Aerospace Engineering, Seoul National University, Seoul, Korea, 3 World Class University (WCU) Program of Multiscale Design, School of Mechanical and Aerospace Engineering, Seoul National University, Seoul, Korea Abstract Even though the disruption of axonal transport is an important pathophysiological factor in neurodegenerative diseases including Alzheimer’s disease (AD), the relationship between disruption of axonal transport and pathogenesis of AD is poorly understood. Considering that a-tubulin acetylation is an important factor in axonal transport and that Ab impairs mitochondrial axonal transport, we manipulated the level of a-tubulin acetylation in hippocampal neurons with Ab cultured in a microfluidic system and examined its effect on mitochondrial axonal transport. We found that inhibiting histone deacetylase 6 (HDAC6), which deacetylates a-tubulin, significantly restored the velocity and motility of the mitochondria in both anterograde and retrograde axonal transports, which would be otherwise compromised by Ab. The inhibition of HDAC6 also recovered the length of the mitochondria that had been shortened by Ab to a normal level. These results suggest that the inhibition of HDAC6 significantly rescues hippocampal neurons from Ab-induced