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Identification of a common non-apoptotic cell death mechanism in hereditary retinal degeneration.

Arango-Gonzalez, Blanca; Trifunović, Dragana; Sahaboglu, Ayse; Kranz, Katharina; Michalakis, Stylianos; Farinelli, Pietro LU ; Koch, Susanne; Koch, Fred; Cottet, Sandra and Janssen-Bienhold, Ulrike, et al. (2014) In PLoS ONE 9(11).
Abstract
Cell death in neurodegenerative diseases is often thought to be governed by apoptosis; however, an increasing body of evidence suggests the involvement of alternative cell death mechanisms in neuronal degeneration. We studied retinal neurodegeneration using 10 different animal models, covering all major groups of hereditary human blindness (rd1, rd2, rd10, Cngb1 KO, Rho KO, S334ter, P23H, Cnga3 KO, cpfl1, Rpe65 KO), by investigating metabolic processes relevant for different forms of cell death. We show that apoptosis plays only a minor role in the inherited forms of retinal neurodegeneration studied, where instead, a non-apoptotic degenerative mechanism common to all mutants is of major importance. Hallmark features of this pathway are... (More)
Cell death in neurodegenerative diseases is often thought to be governed by apoptosis; however, an increasing body of evidence suggests the involvement of alternative cell death mechanisms in neuronal degeneration. We studied retinal neurodegeneration using 10 different animal models, covering all major groups of hereditary human blindness (rd1, rd2, rd10, Cngb1 KO, Rho KO, S334ter, P23H, Cnga3 KO, cpfl1, Rpe65 KO), by investigating metabolic processes relevant for different forms of cell death. We show that apoptosis plays only a minor role in the inherited forms of retinal neurodegeneration studied, where instead, a non-apoptotic degenerative mechanism common to all mutants is of major importance. Hallmark features of this pathway are activation of histone deacetylase, poly-ADP-ribose-polymerase, and calpain, as well as accumulation of cyclic guanosine monophosphate and poly-ADP-ribose. Our work thus demonstrates the prevalence of alternative cell death mechanisms in inherited retinal degeneration and provides a rational basis for the design of mutation-independent treatments. (Less)
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PLoS ONE
volume
9
issue
11
publisher
Public Library of Science
external identifiers
  • pmid:25392995
  • wos:000347709300035
  • scopus:84911489013
ISSN
1932-6203
DOI
10.1371/journal.pone.0112142
language
English
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yes
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de58370d-67fe-4861-b045-15b9bf016e92 (old id 4816798)
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http://www.ncbi.nlm.nih.gov/pubmed/25392995?dopt=Abstract
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2014-12-02 16:29:15
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@article{de58370d-67fe-4861-b045-15b9bf016e92,
  abstract     = {Cell death in neurodegenerative diseases is often thought to be governed by apoptosis; however, an increasing body of evidence suggests the involvement of alternative cell death mechanisms in neuronal degeneration. We studied retinal neurodegeneration using 10 different animal models, covering all major groups of hereditary human blindness (rd1, rd2, rd10, Cngb1 KO, Rho KO, S334ter, P23H, Cnga3 KO, cpfl1, Rpe65 KO), by investigating metabolic processes relevant for different forms of cell death. We show that apoptosis plays only a minor role in the inherited forms of retinal neurodegeneration studied, where instead, a non-apoptotic degenerative mechanism common to all mutants is of major importance. Hallmark features of this pathway are activation of histone deacetylase, poly-ADP-ribose-polymerase, and calpain, as well as accumulation of cyclic guanosine monophosphate and poly-ADP-ribose. Our work thus demonstrates the prevalence of alternative cell death mechanisms in inherited retinal degeneration and provides a rational basis for the design of mutation-independent treatments.},
  articleno    = {e112142},
  author       = {Arango-Gonzalez, Blanca and Trifunović, Dragana and Sahaboglu, Ayse and Kranz, Katharina and Michalakis, Stylianos and Farinelli, Pietro and Koch, Susanne and Koch, Fred and Cottet, Sandra and Janssen-Bienhold, Ulrike and Dedek, Karin and Biel, Martin and Zrenner, Eberhart and Euler, Thomas and Ekström, Per and Ueffing, Marius and Paquet-Durand, Francois},
  issn         = {1932-6203},
  language     = {eng},
  number       = {11},
  publisher    = {Public Library of Science},
  series       = {PLoS ONE},
  title        = {Identification of a common non-apoptotic cell death mechanism in hereditary retinal degeneration.},
  url          = {http://dx.doi.org/10.1371/journal.pone.0112142},
  volume       = {9},
  year         = {2014},
}