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They contribute to a variety of physiological functions and any alteration of the serpin-protease equilibrium can lead to severe consequences. SERPINA3 dysregulation has been associated with Alzheimer\u2019s disease (AD) and prion diseases. In this study, we investigated the differential expression of serpin superfamily members in neurodegenerative diseases.\n                    <jats:italic>SERPIN<\/jats:italic>\n                    expression was analyzed in human frontal cortex samples from cases of sporadic Creutzfeldt-Jakob disease (sCJD), patients at early stages of AD\u2013related pathology, and age-matched controls not affected by neurodegenerative disorders. In addition, we studied whether\n                    <jats:italic>Serpin<\/jats:italic>\n                    expression was dysregulated in two animal models of prion disease and AD.\n                  <\/jats:p>\n                  <jats:p>\n                    Our analysis revealed that, besides the already observed upregulation of\n                    <jats:italic>SERPINA3<\/jats:italic>\n                    in patients with prion disease and AD,\n                    <jats:italic>SERPINB1<\/jats:italic>\n                    ,\n                    <jats:italic>SERPINB6<\/jats:italic>\n                    ,\n                    <jats:italic>SERPING1<\/jats:italic>\n                    ,\n                    <jats:italic>SERPINH1<\/jats:italic>\n                    , and\n                    <jats:italic>SERPINI1<\/jats:italic>\n                    were dysregulated in sCJD individuals compared to controls, while only\n                    <jats:italic>SERPINB1<\/jats:italic>\n                    was upregulated in AD patients. Furthermore, we analyzed whether other serpin members were differentially expressed in prion-infected mice compared to controls and, together with\n                    <jats:italic>SerpinA3n<\/jats:italic>\n                    ,\n                    <jats:italic>SerpinF2<\/jats:italic>\n                    increased levels were observed. Interestingly, SerpinA3n transcript and protein were upregulated in a mouse model of AD. The SERPINA3\/SerpinA3nincreased anti-protease activity found in post-mortem brain tissue of AD and prion disease samples suggest its involvement in the neurodegenerative processes. A SERPINA3\/SerpinA3n role in neurodegenerative disease-related protein aggregation was further corroborated by\n                    <jats:italic>in vitro<\/jats:italic>\n                    SerpinA3n-dependent prion accumulation changes. Our results indicate SERPINA3\/SerpinA3n is a potential therapeutic target for the treatment of prion and prion-like neurodegenerative diseases.\n                  <\/jats:p>","DOI":"10.1007\/s12035-022-02817-3","type":"journal-article","created":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T10:05:38Z","timestamp":1649844338000},"page":"3778-3799","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":75,"title":["Serpin Signatures in Prion and Alzheimer\u2019s Diseases"],"prefix":"10.1007","volume":"59","author":[{"given":"Marco","family":"Zattoni","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marika","family":"Mearelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Vanni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arianna","family":"Colini Baldeschi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thanh Hoa","family":"Tran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Ferracin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcella","family":"Catania","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabio","family":"Moda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Di Fede","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giorgio","family":"Giaccone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabrizio","family":"Tagliavini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianluigi","family":"Zanusso","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James W.","family":"Ironside","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isidre","family":"Ferrer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0716-4393","authenticated-orcid":false,"given":"Giuseppe","family":"Legname","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,4,13]]},"reference":[{"issue":"12","key":"2817_CR1","doi-asserted-by":"publisher","first-page":"1845","DOI":"10.1101\/gr.gr-1478r","volume":"10","author":"JA Irving","year":"2000","unstructured":"Irving JA, Pike RN, Lesk AM, Whisstock JC (2000) Phylogeny of the serpin superfamily: implications of patterns of amino acid conservation for structure and function. 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The use of human tissue provided by the MRC Edinburgh Brain Bank was covered by ethical approval from the East of Scotland Research Ethics Service REC 1 (reference number 16\/ES\/0084). Human brain tissue obtained from the Institute of Neuropathology Brain Bank (HUB-ICO-IDIBELL Biobank, Barcelona, Spain) followed the guidelines of Spanish legislation (Real Decreto 1716\/2011) and the approval of the local ethics committee. This study was approved by the institutional review board of Carlo Besta Neurological Institute and performed according to the guidelines approved by the ethics committee. Brain tissue sample from University Hospital of Verona was obtained following the approval of an ethics committee.All procedures involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted. Current animal husbandry and housing practices comply with the Council of Europe Convention ETS123 (European Convention for the Protection of Vertebrate Animals used for Experimental and Other Scientific Purposes; Strasbourg, 18.03.1986); Italian Legislative Decree 26\/2014, Gazzetta Ufficiale della Repubblica Italiana, 26 July 2014; and with the 86\/609\/EEC (Council Directive of 24 November 1986 on the approximation of laws, regulations, and administrative provisions of the Member States regarding the protection of animals used for experimental and other scientific purposes). The animal facility is licensed and inspected by the Italian Ministry of Health. Mice were housed in groups of 2\u20135 animals in individually ventilated cages, daily fed, and water provided ad libitum. Lighting was on an automatic 12-h basis. All surgery was performed under tribromoethanol anesthesia, and all efforts were made to minimize suffering and regular veterinary care was daily performed for assessment of animal health. The study, including its Ethics requirements, was approved by the Italian Ministry of Health (Permit Number: NP-02\u201314).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics Approval"}},{"value":"Informed consent for participation in research of autopsy tissue was obtained from the relatives of the deceased whenever necessary in accordance with the Declaration of Helsinki (1964\u20132008) and the Additional Protocol on the Convention of Human Rights and Biomedicine concerning Biomedical Research (2005).","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to Participate"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of Interest"}}]}}