Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:2.7.11.12 (
PKG
)
2,515
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
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.
...
PMID:PKG activity causes photoreceptor cell death in two retinitis pigmentosa models. 1918 97
