The prion protein is neuroprotective against retinal degeneration in vivo.
A common feature of neurodegenerative disorders is acute or progressive loss of neurons due to apoptosis. The pathological isoform of the prion protein is associated with retinal apoptosis and the cellular isoform (PrPc) has been shown to mediate protection from apoptosis in cell culture and in neonatal retinal explants. Using a model of light-induced photoreceptor apoptosis, we show in vivo that the levels of PrPc expression in the retina inversely correlate with the susceptibility of photoreceptors to light damage. Dissection of apoptotic signalling cascades suggests that PrPc acts neuroprotectively downstream of AP-1 induction. Our results reveal PrP as a neuroprotective/anti-apoptotic factor in vivo and suggest that PrPc may function as a guardian of neuronal integrity.
Frigg
Rico
R
Lab for Retinal Cell Biology, Department of Ophthalmology, Center for Integrative Human Physiology (CIHP) and Neuroscience Center (ZNZ), University of Zurich, Frauenklinikstrasse 24, Zürich, Switzerland.
Wenzel
Andreas
A
Samardzija
Marijana
M
Oesch
Bruno
B
Wariwoda
Hedwig
H
Navarini
Alexander A
AA
Seeliger
Mathias W
MW
Tanimoto
Naoyuki
N
Remé
Charlotte
C
Grimm
Christian
C
D000818:Animals; D017209:Apoptosis / Q000528:radiation effects; D004198:Disease Susceptibility; D024202:Electrophoretic Mobility Shift Assay; D008027:Light; D051379:Mice; D008807:Mice, Inbred BALB C; D020419:Photoreceptor Cells, Vertebrate / Q000528:radiation effects; D018621:PrPC Proteins / Q000378:metabolism / Q000502:physiology*; D011833:Radiation Injuries, Experimental / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D012160:Retina / Q000378:metabolism; D012162:Retinal Degeneration / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D015398:Signal Transduction / Q000528:radiation effects
D018621:PrPC Proteins