{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T16:33:55Z","timestamp":1777394035883,"version":"3.51.4"},"reference-count":77,"publisher":"SAGE Publications","issue":"1","license":[{"start":{"date-parts":[[2016,1,20]],"date-time":"2016-01-20T00:00:00Z","timestamp":1453248000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Alzheimer\u2019s Disease"],"published-print":{"date-parts":[[2016,2,27]]},"abstract":"<jats:p>\n                    Hemin is known to induce endocytosis of prion-protein (PrP\n                    <jats:sup>C<\/jats:sup>\n                    ) from the neuronal plasma membrane, potentially limiting propagation of the disease causing PrP-scrapie (PrP\n                    <jats:sup>Sc<\/jats:sup>\n                    ) isoform. Hemin is therefore an attractive disease-modifying option for sporadic Creutzfeldt-Jakob disease (sCJD), a human prion disorder with no effective treatment. The hemin-PrP\n                    <jats:sup>C<\/jats:sup>\n                    interaction is also of interest in cerebral-hemorrhage (CH), a condition where potentially toxic hemin molecules come in contact with neuronal PrP\n                    <jats:sup>C<\/jats:sup>\n                    . Interestingly, PrP\n                    <jats:sup>C<\/jats:sup>\n                    is upregulated in penumbric neurons surrounding CH and is known to confer neuroprotection in a dose-dependent manner. The underlying mechanism, however, is not clear. Here, we report that hemin binds PrP\n                    <jats:sup>C<\/jats:sup>\n                    on diverse cell lines, resulting in its aggregation or degradation in a cell-type specific manner. Surprisingly, the hemin-PrP\n                    <jats:sup>C<\/jats:sup>\n                    interaction upregulates Hb synthesis in hematopoietic cells, a response reversed by deleting the hemin-binding octa-peptide repeat region of PrP\n                    <jats:sup>C<\/jats:sup>\n                    . A similar response is noted in brain organotypic cultures where exposure to hemin induces significantly more\n                    <jats:italic toggle=\"yes\">\u03b1<\/jats:italic>\n                    -globin in wild-type (PrP\n                    <jats:sup>+\/+<\/jats:sup>\n                    ) relative to PrP-knock-out (PrP\n                    <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    ) samples. Furthermore, red blood cells and brain tissue from PrP\n                    <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    mice show significantly less\n                    <jats:italic toggle=\"yes\">\u03b1<\/jats:italic>\n                    -globin relative to PrP\n                    <jats:sup>+\/+<\/jats:sup>\n                    controls, indicating a positive effect of PrP\n                    <jats:sup>C<\/jats:sup>\n                    on Hb synthesis under physiological conditions as well. Surprisingly, levels of\n                    <jats:italic toggle=\"yes\">\u03b1<\/jats:italic>\n                    -globin are significantly higher in sCJD brain tissue relative to controls, suggesting compensatory upregulation of Hb synthesis by surviving neurons or misregulation in diseased brains. These observations reveal a unique function of PrP\n                    <jats:sup>C<\/jats:sup>\n                    that is likely to impact the therapeutic management of CH and sCJD.\n                  <\/jats:p>","DOI":"10.3233\/jad-151039","type":"journal-article","created":{"date-parts":[[2016,3,1]],"date-time":"2016-03-01T11:06:43Z","timestamp":1456830403000},"page":"107-121","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":9,"title":["Prion Protein-Hemin Interaction Upregulates Hemoglobin Synthesis: Implications for Cerebral Hemorrhage and Sporadic Creutzfeldt-Jakob Disease"],"prefix":"10.1177","volume":"51","author":[{"given":"Ajai K.","family":"Tripathi","sequence":"first","affiliation":[{"name":"Case Western Reserve University","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Neena","family":"Singh","sequence":"additional","affiliation":[{"name":"Case Western Reserve 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