{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T12:25:44Z","timestamp":1791980744878,"version":"4.4.0"},"reference-count":50,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,6,12]],"date-time":"2025-06-12T00:00:00Z","timestamp":1749686400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100031478","name":"NextGenerationEU","doi-asserted-by":"publisher","award":["CUP E53C24000710006"],"award-info":[{"award-number":["CUP E53C24000710006"]}],"id":[{"id":"10.13039\/100031478","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>The objective of this study was to outline the dynamics of the mitochondrial network and cytoprotective response in patients with Parkinson's disease (PD)\u2010derived olfactory mucosa neurons (ONs) at different disease stages.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      ONs obtained by nasal brush from 41 well\u2010phenotyped patients with PD (n\u2009=\u200924 PD de novo [PD\n                      <jats:sup>dn<\/jats:sup>\n                      ] and n\u2009=\u200917 under treatment [PD\n                      <jats:sup>tr<\/jats:sup>\n                      ]) and 29 healthy controls were examined through real\u2010time polymerase chain reaction (RT\u2010PCR), immunofluorescence, and Western blot. An integrative set of experiments using SH\u2010SY5Y neuronal cells was also performed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      PD ONs accumulated \u03b1\u2010synuclein oligomers in association with an aberrant subcellular distribution of mitochondrial markers COX IV and HSP60. DJ\u20101 ONs expression was permanently reduced in PD, revealing the mitochondrial dysfunction and justifying the defective Nrf2\u2010mediated cytoprotective response. The Nrf2\/SOD\u20101 pathway was indeed downregulated in PD ONs, although with stage\u2010specific differences. In PD\n                      <jats:sup>dn<\/jats:sup>\n                      ONs, Nrf2 mostly presented in the inactive cytosolic localization with a major reduction of SOD\u20101 expression, whereas in PD\n                      <jats:sup>tr<\/jats:sup>\n                      , the Nrf2 active nuclear fraction increased, and the SOD\u20101 expression raised. In SH\u2010SY5Y cells, we demonstrated that dopamine administration increases the Nrf2 nuclear fraction, acting as a possible pathway's inducer.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>Human\u2010derived ONs may recapitulate PD pathogenic milestones, exhibiting stage\u2010specific interactions among \u03b1\u2010synuclein oligomers, mitochondrial metabolism, and cytoprotective response. These findings highlighted mitochondrial dysfunction as a primary target for therapeutic interventions and a potential axis for the biological stratification of patients. Moreover, they supported the translational value of ONs, as a source of biomarkers or models, which is critical in the current changing paradigm of PD toward a biological\u2010based approach. ANN NEUROL 2025;98:699\u2013710<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ana.27292","type":"journal-article","created":{"date-parts":[[2025,6,17]],"date-time":"2025-06-17T08:22:43Z","timestamp":1750148563000},"page":"699-710","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["\u03b1\u2010Synuclein\u2010Related Mitochondria\u2010Nrf2 Dysfunction in Parkinson's Disease Olfactory Mucosa"],"prefix":"10.1002","volume":"98","author":[{"given":"Daniela","family":"Maftei","sequence":"first","affiliation":[{"name":"Unit of Neurology, Department of Systems Medicine Tor Vergata University of Rome  Rome Italy"},{"name":"Unit of Neurology Fondazione PTV \u2013 Tor Vergata University Hospital  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Grazia","family":"Di Certo","sequence":"additional","affiliation":[{"name":"National Research Council (CNR) Institute of Biochemistry and Cell Biology (IBBC)  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riccardo","family":"Maurizi","sequence":"additional","affiliation":[{"name":"Unit of ENT, Department of Clinical Sciences and Translational Medicine Tor Vergata University of Rome  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federica","family":"Veltri","sequence":"additional","affiliation":[{"name":"Unit of Neurology, Department of Systems Medicine Tor Vergata University of Rome  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0952-1710","authenticated-orcid":false,"given":"Marco","family":"Rosina","sequence":"additional","affiliation":[{"name":"Department of Neuroscience Italian National Institute of Health (ISS)  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacopo","family":"Bissacco","sequence":"additional","affiliation":[{"name":"Unit of Neurology, Department of Systems Medicine Tor Vergata University of Rome  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Davide","family":"Mascioli","sequence":"additional","affiliation":[{"name":"Unit of Neurology, Department of Systems Medicine Tor Vergata University of Rome  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta","family":"Bovenzi","sequence":"additional","affiliation":[{"name":"Unit of Neurology, Department of Systems Medicine Tor Vergata University of Rome  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clara","family":"Simonetta","sequence":"additional","affiliation":[{"name":"Unit of Neurology, Department of Systems Medicine Tor Vergata University of Rome  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Mancini","sequence":"additional","affiliation":[{"name":"Unit of Neurology, Department of Systems Medicine Tor Vergata University of Rome  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronica","family":"Buttarazzi","sequence":"additional","affiliation":[{"name":"Unit of Neurology, Department of Systems Medicine Tor Vergata University of Rome  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sveva","family":"Viola","sequence":"additional","affiliation":[{"name":"Unit of ENT, Department of Clinical Sciences and Translational Medicine Tor Vergata University of Rome  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Gravina","sequence":"additional","affiliation":[{"name":"Unit of ENT, Department of Clinical Sciences and Translational Medicine Tor Vergata University of Rome  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Grazia","family":"Maglie","sequence":"additional","affiliation":[{"name":"Unit of ENT, Department of Clinical Sciences and Translational Medicine Tor Vergata University of Rome  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna Maria","family":"Rinaldi","sequence":"additional","affiliation":[{"name":"Unit of Neurology, Department of Systems Medicine Tor Vergata University of Rome  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Gabanella","sequence":"additional","affiliation":[{"name":"National Research Council (CNR) Institute of Biochemistry and Cell Biology (IBBC)  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luciano","family":"Saso","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology \u201cV. 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