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Paquet-Durand, F.* ; Hauck, S.M. ; van Veen, T.* ; Ueffing, M. ; Ekström, P.*

PKG activity causes photoreceptor cell death in two retinitis pigmentosa models.

J. Neurochem. 108, 796-810 (2009)
DOI PMC
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
Photoreceptor degeneration in retinitis pigmentosa is one of the leading causes of hereditary blindness in the developed world. Although causative genetic mutations have been elucidated in many cases, the underlying neuronal degeneration mechanisms are still unknown. Here, we show that activation of cGMP-dependent protein kinase (PKG) hallmarks photoreceptor degeneration in rd1 and rd2 human homologous mouse models. When induced in wild-type retinae, PKG activity was both necessary and sufficient to trigger cGMP-mediated photoreceptor cell death. Target-specific, pharmacological inhibition of PKG activity in both rd1 and rd2 retinae strongly reduced photoreceptor cell death in organotypic retinal explants. Likewise, inhibition of PKG in vivo, using three different application paradigms, resulted in robust photoreceptor protection in the rd1 retina. These findings suggest a pivotal role for PKG activity in cGMP-mediated photoreceptor degeneration mechanisms and highlight the importance of PKG as a novel target for the pharmacological intervention in RP.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter calcium; cGK; cGMP; nitric oxide; rd1 mouse; retina; dependent protein-kinase; vasodilator-stimulated phosphoprotein; inherited retinal degenerations; rod cgmp-phosphodiesterase; nucleotide-gated channels; d-cis-diltiazem; cyclic-gmp; mouse retina; rd mouse; guanosine-monophosphate
Sprache englisch
Veröffentlichungsjahr 2009
HGF-Berichtsjahr 2009
ISSN (print) / ISBN 0022-3042
e-ISSN 1471-4159
Zeitschrift Journal of Neurochemistry
Quellenangaben Band: 108, Heft: 3, Seiten: 796-810 Artikelnummer: , Supplement: ,
Verlag Wiley
Begutachtungsstatus Peer reviewed
Institut(e) CF Metabolomics & Proteomics (CF-MPC)
POF Topic(s) 30203 - Molecular Targets and Therapies
Forschungsfeld(er) Enabling and Novel Technologies
PSP-Element(e) G-505700-001
PubMed ID 19187097
DOI 10.1111/j.1471-4159.2008.05822.x
Scopus ID 58149333254
Erfassungsdatum 2009-12-31
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