{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T05:31:57Z","timestamp":1790227917788,"version":"4.1.0"},"reference-count":51,"publisher":"Society for Neuroscience","issue":"19","license":[{"start":{"date-parts":[[2007,11,9]],"date-time":"2007-11-09T00:00:00Z","timestamp":1194566400000},"content-version":"vor","delay-in-days":184,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Neurosci."],"published-print":{"date-parts":[[2007,5,9]]},"abstract":"<jats:p>Prion protein (PrP) inhibits the activation of proapoptotic Bax in primary human neurons and MCF-7 cells. Because neuronal apoptosis occurs in human prion diseases, here we examine the anti-Bax function of familial PrP mutants. All Creutzfeldt-Jakob disease and fatal familial insomnia-associated prion protein mutations partially or completely lose the anti-Bax function in human neurons and, except for A117V and V203I, in MCF-7 cells. The ability of the mutants to protect against Bax-mediated cell death is divided into three groups: (1) group I, retention of anti-Bax function in both the Val<jats:sup>129<\/jats:sup>and Met<jats:sup>129<\/jats:sup>mutants; (2) group II, retention of anti-Bax function only in Val<jats:sup>129<\/jats:sup>mutants; and (3) group III, reduction or no anti-Bax function in Val<jats:sup>129<\/jats:sup>and Met<jats:sup>129<\/jats:sup>mutants. The loss of anti-Bax function in these PrP mutants correlates completely with a significant decrease in the production of cytosolic PrP, a form of PrP shown previously to have anti-Bax function in human neurons. Cotransfection of the full-length PrP mutants with wild-type or mutant cytosolic PrP, but not with wild type full-length PrP, rescues the anti-Bax function of PrP. The results show that the failure of PrP mutants to produce cytosolic PrP is responsible for the loss of anti-Bax function and that the effect of the PrP mutants is dominant over wild-type PrP. Furthermore, these results imply that misfolded PrP that escapes retrotranslocation could accumulate at the cell surface and cause neuronal dysfunction.<\/jats:p>","DOI":"10.1523\/jneurosci.0957-07.2007","type":"journal-article","created":{"date-parts":[[2007,5,9]],"date-time":"2007-05-09T17:14:28Z","timestamp":1178730868000},"page":"5081-5091","source":"Crossref","is-referenced-by-count":18,"title":["Defective Retrotranslocation Causes Loss of Anti-Bax Function in Human Familial Prion Protein Mutants"],"prefix":"10.1523","volume":"27","author":[{"given":"Julie","family":"Jodoin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"St\u00e9phanie","family":"Laroche-Pierre","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cynthia G.","family":"Goodyer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9a 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