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

Chaeyoung Kim, Heesun Choi, Eun Sun Jung, Wonik Lee, Soojung Oh, Noo Li Jeon, Inhee Mook-Jung

Research output: Contribution to journalArticle

61 Citations (Scopus)

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 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.

Original languageEnglish
Article numbere42983
JournalPLoS ONE
Volume7
Issue number8
DOIs
StatePublished - 22 Aug 2012

Fingerprint

histone deacetylase
Axonal Transport
Histone Deacetylase Inhibitors
Histone Deacetylases
amyloid
Amyloid
Neurons
Tubulin
neurons
Acetylation
Mitochondria
tubulin
Neurodegenerative diseases
acetylation
Alzheimer disease
Microfluidics
Alzheimer Disease
mitochondria
Elongation
Mitochondrial Dynamics

Cite this

Kim, Chaeyoung ; Choi, Heesun ; Jung, Eun Sun ; Lee, Wonik ; Oh, Soojung ; Jeon, Noo Li ; Mook-Jung, Inhee. / HDAC6 inhibitor blocks amyloid beta-induced impairment of mitochondrial transport in hippocampal neurons. In: PLoS ONE. 2012 ; Vol. 7, No. 8.
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HDAC6 inhibitor blocks amyloid beta-induced impairment of mitochondrial transport in hippocampal neurons. / Kim, Chaeyoung; Choi, Heesun; Jung, Eun Sun; Lee, Wonik; Oh, Soojung; Jeon, Noo Li; Mook-Jung, Inhee.

In: PLoS ONE, Vol. 7, No. 8, e42983, 22.08.2012.

Research output: Contribution to journalArticle

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