HDAC6 Inhibitor Blocks Amyloid Beta-Induced Impairment of MitochondrialTransport in Hippocampal Neurons

Collection with item attached
2012
Item details URL
http://open-repository.kisti.re.kr/cube/handle/open_repository/479754.do
DOI
10.1371/journal.pone.0042983
Title
HDAC6 Inhibitor Blocks Amyloid Beta-Induced Impairment of MitochondrialTransport in Hippocampal Neurons
Description
This work was supported by grants from the 21C Frontier FunctionalProteomics Project (FPR08K1301-02210), National Research Foundation2009-0081673, World Class University-Neurocytomics, and the KoreanNational Institute of Health R&D Program Project (2009-0443) andsupported in part by the Basic Research Program (2008-05943) and MRC atSNU (2011-0030738). The funders had no role in study design, datacollection and analysis, decision to publish, or preparation of themanuscript.
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 alpha-tubulin acetylation is an important factor in axonal transport and that A beta impairs mitochondrial axonal transport, we manipulated the level of alpha-tubulin acetylation in hippocampal neurons with A beta cultured in a microfluidic system and examined its effect on mitochondrial axonal transport. We found that inhibiting histone deacetylase 6 (HDAC6), which deacetylates alpha-tubulin, significantly restored the velocity and motility of the mitochondria in both anterograde and retrograde axonal transports, which would be otherwise compromised by A beta. The inhibition of HDAC6 also recovered the length of the mitochondria that had been shortened by A beta to a normal level. These results suggest that the inhibition of HDAC6 significantly rescues hippocampal neurons from A beta-induced impairment of mitochondrial axonal transport as well as mitochondrial length. The results presented in this paper identify HDAC6 as an important regulator of mitochondrial transport as well as elongation and, thus, a potential target whose pharmacological inhibition contributes to improving mitochondrial dynamics in Ab treated neurons.
provenance
Made available in Cube on 2018-09-28T13:07:52Z (GMT). No. of bitstreams: 0
language
English
author
Kim, Chaeyoung
Choi, Heesun
Jung, Eun Sun
Lee, Wonik
Oh, Soojung
Jeon, Noo Li
Mook-Jung, Inhee
orcid
Beck, Michael/0000-0002-5107-9973
accessioned
2018-09-28T13:07:52Z
available
2018-09-28T13:07:52Z
issued
2012
citation
PLOS ONE(7): 8
issn
1932-6203
uri
http://open-repository.kisti.re.kr/cube/handle/open_repository/479754.do
Funder
교육과학기술부
Funding Program
2단계연구중심대학육성(0.5)
Project ID
1345196656
Jurisdiction
Rep.of Korea
Project Name
차세대 기계항공시스템 창의설계 인력양성사어단
rights
openAccess
type
article


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