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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

Title
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
Authors
Kim, Ji-YonWoo, So-YounHong, Young BinChoi, HeesunKim, JisooChoi, HyunjungMook-Jung, InheeHa, NinaKyung, JangbeenKoo, Soo KyungJung, Sung-ChulChoi, Byung-Ok
Ewha Authors
우소연정성철
SCOPUS Author ID
우소연scopus; 정성철scopus
Issue Date
2016
Journal Title
STEM CELLS INTERNATIONAL
ISSN
1687-966XJCR Link1687-9678JCR Link
Publisher
HINDAWI PUBLISHING CORP
Indexed
SCIE WOS
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 alpha-tubulin acetylation compared with controls. The newly developed HDAC6 inhibitors, CHEMICAL X4 and CHEMICAL X9, increased acetylation of alpha-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.
DOI
10.1155/2016/9475981
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의과대학 > 의학과 > Journal papers
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