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Excessive HDAC activation is critical for neurodegeneration in the rd1 mouse

Sancho-Pelluz, J.; Alavi, Marcel LU ; Sahaboglu, A.; Kustermann, S.; Farinelli, Pietro LU ; Azadi, S.; van Veen, Theo LU ; Romero, F. J.; Paquet-Durand, F. and Ekström, Per LU (2010) In Cell Death & Disease 1.
Abstract
Inherited retinal degenerations, collectively termed retinitis pigmentosa (RP), constitute one of the leading causes of blindness in the developed world. RP is at present untreatable and the underlying neurodegenerative mechanisms are unknown, even though the genetic causes are often established. Acetylation and deacetylation of histones, carried out by histone acetyltransferases (HATs) and histone deacetylases (HDACs), respectively, affects cellular division, differentiation, death and survival. We found acetylation of histones and probably other proteins to be dramatically reduced in degenerating photoreceptors in the rd1 human homologous mouse model for RP. Using a custom developed in situ HDAC activity assay, we show that... (More)
Inherited retinal degenerations, collectively termed retinitis pigmentosa (RP), constitute one of the leading causes of blindness in the developed world. RP is at present untreatable and the underlying neurodegenerative mechanisms are unknown, even though the genetic causes are often established. Acetylation and deacetylation of histones, carried out by histone acetyltransferases (HATs) and histone deacetylases (HDACs), respectively, affects cellular division, differentiation, death and survival. We found acetylation of histones and probably other proteins to be dramatically reduced in degenerating photoreceptors in the rd1 human homologous mouse model for RP. Using a custom developed in situ HDAC activity assay, we show that overactivation of HDAC classes I/II temporally precedes photoreceptor degeneration. Moreover, pharmacological inhibition of HDACs I/II activity in rd1 organotypic retinal explants decreased activity of poly-ADP-ribose-polymerase and strongly reduced photoreceptor cell death. These findings highlight the importance of protein acetylation for photoreceptor cell death and survival and propose certain HDAC classes as novel targets for the pharmacological intervention in RP. Cell Death and Disease (2010) 1, e24; doi:10.1038/cddis.2010.4; published online 11 February 2010 (Less)
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author
organization
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type
Contribution to journal
publication status
published
subject
keywords
sirtuin, retina, trichostatin A, epigenetic, neuroprotection, retinitis, pigmentosa
in
Cell Death & Disease
volume
1
publisher
Nature Publishing Group
external identifiers
  • wos:000279616500004
  • scopus:77958558027
ISSN
2041-4889
DOI
10.1038/cddis.2010.4
language
English
LU publication?
yes
id
c3ad0836-d2f9-4a06-8892-0a37c3533906 (old id 1658020)
date added to LUP
2010-08-20 08:39:54
date last changed
2018-05-29 12:13:29
@article{c3ad0836-d2f9-4a06-8892-0a37c3533906,
  abstract     = {Inherited retinal degenerations, collectively termed retinitis pigmentosa (RP), constitute one of the leading causes of blindness in the developed world. RP is at present untreatable and the underlying neurodegenerative mechanisms are unknown, even though the genetic causes are often established. Acetylation and deacetylation of histones, carried out by histone acetyltransferases (HATs) and histone deacetylases (HDACs), respectively, affects cellular division, differentiation, death and survival. We found acetylation of histones and probably other proteins to be dramatically reduced in degenerating photoreceptors in the rd1 human homologous mouse model for RP. Using a custom developed in situ HDAC activity assay, we show that overactivation of HDAC classes I/II temporally precedes photoreceptor degeneration. Moreover, pharmacological inhibition of HDACs I/II activity in rd1 organotypic retinal explants decreased activity of poly-ADP-ribose-polymerase and strongly reduced photoreceptor cell death. These findings highlight the importance of protein acetylation for photoreceptor cell death and survival and propose certain HDAC classes as novel targets for the pharmacological intervention in RP. Cell Death and Disease (2010) 1, e24; doi:10.1038/cddis.2010.4; published online 11 February 2010},
  author       = {Sancho-Pelluz, J. and Alavi, Marcel and Sahaboglu, A. and Kustermann, S. and Farinelli, Pietro and Azadi, S. and van Veen, Theo and Romero, F. J. and Paquet-Durand, F. and Ekström, Per},
  issn         = {2041-4889},
  keyword      = {sirtuin,retina,trichostatin A,epigenetic,neuroprotection,retinitis,pigmentosa},
  language     = {eng},
  publisher    = {Nature Publishing Group},
  series       = {Cell Death & Disease},
  title        = {Excessive HDAC activation is critical for neurodegeneration in the rd1 mouse},
  url          = {http://dx.doi.org/10.1038/cddis.2010.4},
  volume       = {1},
  year         = {2010},
}