title: Neuroprotective effects of the cellular prion protein in autoimmune optic neuritis.
abstract: Although the pathologic role of the prion protein in transmissible spongiform encephalopathic diseases has been widely investigated, the physiologic role of the cellular prion protein (PrP(C)) is not known. Among the many functions attributed to PrP(C), there is increasing evidence that it is involved in cell survival and mediates neuroprotection. A potential role in the immune response has also been suggested. However, how these two functions interplay in autoimmune disease is unclear. To address this, autoimmune optic neuritis, a model of multiple sclerosis, was induced in C57Bl/6 mice, and up-regulation of PrP(C) was observed throughout the disease course. In addition, compared with wild-type mice, in PrP(C)-deficient mice and mice overexpressing PrP(C), histopathologic analysis demonstrated that optic neuritis was exacerbated, as indicated by axonal degeneration, inflammatory infiltration, and demyelination. However, significant neuroprotection of retinal ganglion cells, the axons of which form the optic nerve, was observed in mice that overexpressed PrP(C). Conversely, mice lacking PrP(C) demonstrated significantly more neurodegeneration. This suggests that PrP(C) may have a neuroprotective function independent of its role in regulating the immune response.
authors.affiliation: Department of Neurology, University of the Saarland, Homburg/Saar, Germany. sarah.williams@uks.eu
authors.forename: Sarah K
authors.initials: SK
authors.lastname: Williams
authors.forename: Richard
authors.initials: R
authors.lastname: Fairless
authors.forename: Jens
authors.initials: J
authors.lastname: Weise
authors.forename: Ulrich
authors.initials: U
authors.lastname: Kalinke
authors.forename: Walter
authors.initials: W
authors.lastname: Schulz-Schaeffer
authors.forename: Ricarda
authors.initials: R
authors.lastname: Diem
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000150:complications* / Q000473:pathology*; D001369:Axons / Q000187:drug effects / Q000473:pathology; D019610:Cytoprotection / Q000187:drug effects; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000150:complications / Q000473:pathology; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009410:Nerve Degeneration / Q000150:complications / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009900:Optic Nerve / Q000187:drug effects / Q000473:pathology; D009902:Optic Neuritis / Q000150:complications* / Q000473:pathology*; D011328:Prions / Q000378:metabolism*; D012165:Retinal Ganglion Cells / Q000187:drug effects / Q000473:pathology; D012720:Severity of Illness Index; D015398:Signal Transduction / Q000187:drug effects; D013116:Spinal Cord / Q000187:drug effects / Q000473:pathology; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D018696:Neuroprotective Agents; D011328:Prions