{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T03:47:36Z","timestamp":1777434456997,"version":"3.51.4"},"reference-count":183,"publisher":"SAGE Publications","issue":"3","license":[{"start":{"date-parts":[[2014,7,1]],"date-time":"2014-07-01T00:00:00Z","timestamp":1404172800000},"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":["Antioxidants &amp; Redox Signaling"],"published-print":{"date-parts":[[2014,7]]},"abstract":"<jats:p>\n                    <jats:bold>\n                      <jats:italic toggle=\"yes\">Significance:<\/jats:italic>\n                    <\/jats:bold>\n                    Intracellular and extracellular aggregation of a specific protein or protein fragments is the principal pathological event in several neurodegenerative conditions. We describe two such conditions: sporadic Creutzfeldt\u2013Jakob disease (sCJD), a rare but potentially infectious and invariably fatal human prion disorder, and Parkinson's disease (PD), a common neurodegenerative condition second only to Alzheimer's disease in prevalence. In sCJD, a cell surface glycoprotein known as the prion protein (PrP\n                    <jats:sup>C<\/jats:sup>\n                    ) undergoes a conformational change to PrP-scrapie, a pathogenic and infectious isoform that accumulates in the brain parenchyma as insoluble aggregates. In PD, \u03b1-synuclein, a cytosolic protein, forms insoluble aggregates that accumulate in neurons of the substantia nigra and cause neurotoxicity.\n                    <jats:bold>\n                      <jats:italic toggle=\"yes\">Recent Advances:<\/jats:italic>\n                    <\/jats:bold>\n                    Although distinct processes are involved in the pathogenesis of sCJD and PD, both share brain iron dyshomeostasis as a common associated feature that is reflected in the cerebrospinal fluid in a disease-specific manner.\n                    <jats:bold>\n                      <jats:italic toggle=\"yes\">Critical Issues:<\/jats:italic>\n                    <\/jats:bold>\n                    Since PrP\n                    <jats:sup>C<\/jats:sup>\n                    and \u03b1-synuclein play a significant role in maintaining cellular iron homeostasis, it is important to understand whether the aggregation of these proteins and iron dyshomeostasis are causally related. Here, we discuss recent information on the normal function of PrP\n                    <jats:sup>C<\/jats:sup>\n                    and \u03b1-synuclein in cellular iron metabolism and the cellular and biochemical processes that contribute to iron imbalance in sCJD and PD.\n                    <jats:bold>\n                      <jats:italic toggle=\"yes\">Future Directions:<\/jats:italic>\n                    <\/jats:bold>\n                    Improved understanding of the relationship between brain iron imbalance and protein aggregation is likely to help in the development of therapeutic strategies that can restore brain iron homeostasis and mitigate neurotoxicity.\n                    <jats:italic toggle=\"yes\">Antioxid. Redox Signal.<\/jats:italic>\n                    21, 471\u2013484.\n                  <\/jats:p>","DOI":"10.1089\/ars.2014.5874","type":"journal-article","created":{"date-parts":[[2014,2,10]],"date-time":"2014-02-10T10:10:34Z","timestamp":1392027034000},"page":"471-484","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":34,"title":["Iron in Neurodegenerative Disorders of Protein Misfolding: A Case of Prion Disorders and Parkinson's Disease"],"prefix":"10.1177","volume":"21","author":[{"given":"Neena","family":"Singh","sequence":"first","affiliation":[{"name":"Case Western Reserve University"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Swati","family":"Haldar","sequence":"additional","affiliation":[{"name":"Case Western Reserve University"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ajai K.","family":"Tripathi","sequence":"additional","affiliation":[{"name":"Case Western Reserve 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