HDAC6 inhibitor blocks amyloid beta-induced impairment of mitochondrial transport in hippocampal neurons.

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 α-tubulin acetylation...

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Main Authors: Chaeyoung Kim, Heesun Choi, Eun Sun Jung, Wonik Lee, Soojung Oh, Noo Li Jeon, Inhee Mook-Jung
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2012-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC3425572?pdf=render
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author Chaeyoung Kim
Heesun Choi
Eun Sun Jung
Wonik Lee
Soojung Oh
Noo Li Jeon
Inhee Mook-Jung
author_facet Chaeyoung Kim
Heesun Choi
Eun Sun Jung
Wonik Lee
Soojung Oh
Noo Li Jeon
Inhee Mook-Jung
author_sort Chaeyoung Kim
collection DOAJ
description 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 α-tubulin acetylation is an important factor in axonal transport and that Aβ impairs mitochondrial axonal transport, we manipulated the level of α-tubulin acetylation in hippocampal neurons with Aβ cultured in a microfluidic system and examined its effect on mitochondrial axonal transport. We found that inhibiting histone deacetylase 6 (HDAC6), which deacetylates α-tubulin, significantly restored the velocity and motility of the mitochondria in both anterograde and retrograde axonal transports, which would be otherwise compromised by Aβ. The inhibition of HDAC6 also recovered the length of the mitochondria that had been shortened by Aβ to a normal level. These results suggest that the inhibition of HDAC6 significantly rescues hippocampal neurons from Aβ-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 Aβ treated neurons.
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spelling doaj.art-b010d0d1bcdb4174a6d5ea9d1196f76e2022-12-21T19:34:09ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0178e4298310.1371/journal.pone.0042983HDAC6 inhibitor blocks amyloid beta-induced impairment of mitochondrial transport in hippocampal neurons.Chaeyoung KimHeesun ChoiEun Sun JungWonik LeeSoojung OhNoo Li JeonInhee Mook-JungEven 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 α-tubulin acetylation is an important factor in axonal transport and that Aβ impairs mitochondrial axonal transport, we manipulated the level of α-tubulin acetylation in hippocampal neurons with Aβ cultured in a microfluidic system and examined its effect on mitochondrial axonal transport. We found that inhibiting histone deacetylase 6 (HDAC6), which deacetylates α-tubulin, significantly restored the velocity and motility of the mitochondria in both anterograde and retrograde axonal transports, which would be otherwise compromised by Aβ. The inhibition of HDAC6 also recovered the length of the mitochondria that had been shortened by Aβ to a normal level. These results suggest that the inhibition of HDAC6 significantly rescues hippocampal neurons from Aβ-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 Aβ treated neurons.http://europepmc.org/articles/PMC3425572?pdf=render
spellingShingle Chaeyoung Kim
Heesun Choi
Eun Sun Jung
Wonik Lee
Soojung Oh
Noo Li Jeon
Inhee Mook-Jung
HDAC6 inhibitor blocks amyloid beta-induced impairment of mitochondrial transport in hippocampal neurons.
PLoS ONE
title HDAC6 inhibitor blocks amyloid beta-induced impairment of mitochondrial transport in hippocampal neurons.
title_full HDAC6 inhibitor blocks amyloid beta-induced impairment of mitochondrial transport in hippocampal neurons.
title_fullStr HDAC6 inhibitor blocks amyloid beta-induced impairment of mitochondrial transport in hippocampal neurons.
title_full_unstemmed HDAC6 inhibitor blocks amyloid beta-induced impairment of mitochondrial transport in hippocampal neurons.
title_short HDAC6 inhibitor blocks amyloid beta-induced impairment of mitochondrial transport in hippocampal neurons.
title_sort hdac6 inhibitor blocks amyloid beta induced impairment of mitochondrial transport in hippocampal neurons
url http://europepmc.org/articles/PMC3425572?pdf=render
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