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

Authors: Kim, C  Choi, H  Jung, ES  Lee, W  Oh, S  Jeon, NL  Mook-Jung, I 
Citation: Kim C, etal., PLoS One. 2012;7(8):e42983. doi: 10.1371/journal.pone.0042983. Epub 2012 Aug 22.
Pubmed: (View Article at PubMed) PMID:22937007
DOI: Full-text: DOI:10.1371/journal.pone.0042983

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 Abeta impairs mitochondrial axonal transport, we manipulated the level of alpha-tubulin acetylation in hippocampal neurons with Abeta 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 Abeta. The inhibition of HDAC6 also recovered the length of the mitochondria that had been shortened by Abeta to a normal level. These results suggest that the inhibition of HDAC6 significantly rescues hippocampal neurons from Abeta-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 Abeta treated neurons.


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CRRD ID: 9681555
Created: 2014-12-03
Species: All species
Last Modified: 2014-12-03
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.