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

Murine Autoimmune Optic Neuritis Is Not Phenotypically Altered by the Retinal Degeneration 8 Mutation

“…In healthy controls and prior to immunization, RGCs were retrogradely labeled with fluorogold (FG; Fluorochrome LLC, Denver, CO, USA), and disease was induced as previously described. 11,19 Briefly, the mice were immunized with 200 lg myelin oligodendrocyte glycoprotein 35-55 and weighed and scored on a daily basis, with disease severity assessed using a scale ranging from 0 to 5. EAE experiments were performed on 2 separate occasions.…”

“…29 Antibodies against Mac-3 (1:200, BD Biosciences, San Jose, CA, USA) and CD3 (1:150, Dako, Glostrup, Denmark) were used to detect activated microglia/macrophages and T cells, respectively, using previously described protocols. 11,19 For all histopathologic and immunohistochemical investigations, a minimum of 10 sections taken throughout the length of each optic nerve were quantified.…”

“…It is defined as inflammation of the optic nerve that results in a decrease in visual acuity through both demyelination and axonal loss within the optic nerves as well as a loss of retinal ganglion cell (RGC) bodies in the retina. AON can be modeled in both mice [11][12][13] and rats 14,15 through immunization with immunogens, such as myelin oligodendrocyte glycoprotein. This results in a reproducible disease that recapitulates many of the features of the human disease, helping to overcome the problem of limited tissue availability from the acute phase of MS. As an experimental model, it has also proven itself to be a valuable tool for assessing the efficacy of therapeutic strategies prior to translation into clinical trials.…”

“…This results in a reproducible disease that recapitulates many of the features of the human disease, helping to overcome the problem of limited tissue availability from the acute phase of MS. As an experimental model, it has also proven itself to be a valuable tool for assessing the efficacy of therapeutic strategies prior to translation into clinical trials. [16][17][18][19] Furthermore, the ability to model AON in rodents means that genetically engineered iovs.arvojournals.org j ISSN: 1552-5783 mouse strains can be used to provide further insights into neurodegeneration in MS. 11,19,20 However, because of the potential complication of the rd8 mutation arising in such strains, an assessment is necessary. In particular, because many genetically modified mouse lines have been derived using a C57BL/6N background 21 and studies of AON have already been performed on some of these lines, 11 or even on C57BL6 mice of an undefined substrain identity, 20,22,23,24 such an assessment would allow readers to know whether one can have confidence in data obtained from such studies.…”

Structure analysis of human Prion protein involved in Sporadic Fatal Insomnia

“…The ultimate passage from gut through the bloodstream may not require microbial action, but could be facilitated by the prion's own small size, and the trophic ability to reach and access the blood brain barrier (BBB) may be eased by mimesis (7). TSE have often also been classified as autoimmune diseases, not only for their inflammatory and degenerative 'quality' (8), but because they have been linked to the processes of neuroprotection and autoimmunity (9).…”