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Stem Cells International
Volume 2016, Article ID 9475981, 14 pages
http://dx.doi.org/10.1155/2016/9475981
Research Article

HDAC6 Inhibitors Rescued the Defective Axonal Mitochondrial Movement in Motor Neurons Derived from the Induced Pluripotent Stem Cells of Peripheral Neuropathy Patients with HSPB1 Mutation

1Department of Microbiology, School of Medicine, Ewha Womans University, Seoul, Republic of Korea
2Stem Cell & Regenerative Medicine Institute, Samsung Medical Center, Seoul, Republic of Korea
3Department of Biochemistry and Biomedical Sciences, College of Medicine, Seoul National University, Seoul, Republic of Korea
4Chong Kun Dang Research Institute, Yongin-si, Gyeonggi-do, Republic of Korea
5Division of Intractable Diseases, Center for Biomedical Sciences, National Institute of Health, Chungcheongbuk-do, Republic of Korea
6Department of Biochemistry, School of Medicine, Ewha Womans University, Seoul, Republic of Korea
7Departments of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea

Received 18 July 2016; Revised 11 November 2016; Accepted 22 November 2016

Academic Editor: Yang D. Teng

Copyright © 2016 Ji-Yon Kim et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

The Charcot-Marie-Tooth disease 2F (CMT2F) and distal hereditary motor neuropathy 2B (dHMN2B) are caused by autosomal dominantly inherited mutations of the heat shock 27 kDa protein 1 (HSPB1) gene and there are no specific therapies available yet. Here, we assessed the potential therapeutic effect of HDAC6 inhibitors on peripheral neuropathy with HSPB1 mutation using in vitro model of motor neurons derived from induced pluripotent stem cells (iPSCs) of CMT2F and dHMN2B patients. The absolute velocity of mitochondrial movements and the percentage of moving mitochondria in axons were lower both in CMT2F-motor neurons and in dHMN2B-motor neurons than those in controls, and the severity of the defective mitochondrial movement was different between the two disease models. CMT2F-motor neurons and dHMN2B-motor neurons also showed reduced -tubulin acetylation compared with controls. The newly developed HDAC6 inhibitors, CHEMICAL X4 and CHEMICAL X9, increased acetylation of -tubulin and reversed axonal movement defects of mitochondria in CMT2F-motor neurons and dHMN2B-motor neurons. Our results suggest that the neurons derived from patient-specific iPSCs can be used in drug screening including HDAC6 inhibitors targeting peripheral neuropathy.