{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T03:41:49Z","timestamp":1784000509633,"version":"3.55.0"},"reference-count":60,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2017,11,15]],"date-time":"2017-11-15T00:00:00Z","timestamp":1510704000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2017,11,15]],"date-time":"2017-11-15T00:00:00Z","timestamp":1510704000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Prion diseases are fatal neurodegenerative disorders with sporadic, genetic or acquired etiologies. The molecular alterations leading to the onset and the spreading of these diseases are still unknown. In a previous work we identified a five-gene signature able to distinguish intracranially BSE-infected macaques from healthy ones, with <jats:italic>SERPINA3<\/jats:italic> showing the most prominent dysregulation. We analyzed 128 suitable frontal cortex samples, from prion-affected patients (variant Creutzfeldt-Jakob disease (vCJD) n\u2009=\u200920, iatrogenic CJD (iCJD) n\u2009=\u200911, sporadic CJD (sCJD) n\u2009=\u200923, familial CJD (gCJD) n\u2009=\u200917, fatal familial insomnia (FFI) n\u2009=\u20099, Gerstmann\u2013Str\u00e4ussler\u2013Scheinker syndrome (GSS)) n\u2009=\u20094), patients with Alzheimer disease (AD, n\u2009=\u200914) and age-matched controls (n\u2009=\u200930). Real Time-quantitative PCR was performed for <jats:italic>SERPINA3<\/jats:italic> transcript, and <jats:italic>ACTB<\/jats:italic>, <jats:italic>RPL19<\/jats:italic>, <jats:italic>GAPDH<\/jats:italic> and <jats:italic>B2M<\/jats:italic> were used as reference genes. We report <jats:italic>SERPINA3<\/jats:italic> to be strongly up-regulated in the brain of all human prion diseases, with only a mild up-regulation in AD. We show that this striking up-regulation, both at the mRNA and at the protein level, is present in all types of human prion diseases analyzed, although to a different extent for each specific disorder. Our data suggest that <jats:italic>SERPINA3<\/jats:italic> may be involved in the pathogenesis and the progression of prion diseases, representing a valid tool for distinguishing different forms of these disorders in humans.<\/jats:p>","DOI":"10.1038\/s41598-017-15778-8","type":"journal-article","created":{"date-parts":[[2017,11,9]],"date-time":"2017-11-09T12:23:33Z","timestamp":1510230213000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":53,"title":["Differential overexpression of SERPINA3 in human prion diseases"],"prefix":"10.1038","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1192-7322","authenticated-orcid":false,"given":"S.","family":"Vanni","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F.","family":"Moda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Zattoni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E.","family":"Bistaffa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E.","family":"De Cecco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Rossi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G.","family":"Giaccone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F.","family":"Tagliavini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Ha\u00efk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. P.","family":"Deslys","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G.","family":"Zanusso","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. W.","family":"Ironside","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I.","family":"Ferrer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3841-5511","authenticated-orcid":false,"given":"G. G.","family":"Kovacs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0716-4393","authenticated-orcid":false,"given":"G.","family":"Legname","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,11,15]]},"reference":[{"key":"15778_CR1","doi-asserted-by":"publisher","first-page":"601","DOI":"10.1146\/annurev-genet-110711-155524","volume":"47","author":"SB Prusiner","year":"2013","unstructured":"Prusiner, S. B. Biology and genetics of prions causing neurodegeneration. Annu Rev Genet \n                           47, 601\u2013623, https:\/\/doi.org\/10.1146\/annurev-genet-110711-155524 (2013).","journal-title":"Annu Rev Genet"},{"key":"15778_CR2","first-page":"102","volume":"44","author":"JG Collee","year":"2006","unstructured":"Collee, J. G., Bradley, R. & Liberski, P. P. Variant CJD (vCJD) and bovine spongiform encephalopathy (BSE): 10 and 20 years on: part 2. Folia Neuropathol \n                           44, 102\u2013110 (2006). doi:6212 [pii].","journal-title":"Folia Neuropathol"},{"key":"15778_CR3","doi-asserted-by":"publisher","first-page":"292","DOI":"10.1056\/NEJMc1610003","volume":"376","author":"T Mok","year":"2017","unstructured":"Mok, T. et al. Variant Creutzfeldt-Jakob Disease in a Patient with Heterozygosity at PRNP Codon 129. N Engl J Med \n                           376, 292\u2013294, https:\/\/doi.org\/10.1056\/NEJMc1610003 (2017).","journal-title":"N Engl J Med"},{"key":"15778_CR4","doi-asserted-by":"publisher","first-page":"f5675","DOI":"10.1136\/bmj.f5675","volume":"347","author":"ON Gill","year":"2013","unstructured":"Gill, O. N. et al. Prevalent abnormal prion protein in human appendixes after bovine spongiform encephalopathy epizootic: large scale survey. BMJ \n                           347, f5675, https:\/\/doi.org\/10.1136\/bmj.f5675 (2013).","journal-title":"BMJ"},{"key":"15778_CR5","unstructured":"Advisory Committee on Dangerous Pathogens TSE Risk Assessment Subgroup (August 2016). \u201cAppendix-III\u201d position statement. Available from: ACDP TSE subgroup minutes, agendas and papers, https:\/\/app.box.com\/s\/hhhhg857fjpu2bnxhv6e (2016)."},{"key":"15778_CR6","doi-asserted-by":"publisher","first-page":"733","DOI":"10.1002\/path.1580","volume":"203","author":"DA Hilton","year":"2004","unstructured":"Hilton, D. A. et al. Prevalence of lymphoreticular prion protein accumulation in UK tissue samples. J Pathol \n                           203, 733\u2013739, https:\/\/doi.org\/10.1002\/path.1580 (2004).","journal-title":"J Pathol"},{"key":"15778_CR7","doi-asserted-by":"publisher","first-page":"302","DOI":"10.1097\/WCO.0000000000000197","volume":"28","author":"MO Kim","year":"2015","unstructured":"Kim, M. O. & Geschwind, M. D. Clinical update of Jakob-Creutzfeldt disease. Current opinion in neurology \n                           28, 302\u2013310, https:\/\/doi.org\/10.1097\/WCO.0000000000000197 (2015).","journal-title":"Current opinion in neurology"},{"key":"15778_CR8","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1016\/S0140-6736(04)15486-X","volume":"363","author":"CA Llewelyn","year":"2004","unstructured":"Llewelyn, C. A. et al. Possible transmission of variant Creutzfeldt-Jakob disease by blood transfusion. Lancet \n                           363, 417\u2013421, https:\/\/doi.org\/10.1016\/S0140-6736(04)15486-X (2004).","journal-title":"Lancet"},{"key":"15778_CR9","doi-asserted-by":"publisher","first-page":"527","DOI":"10.1016\/S0140-6736(04)16811-6","volume":"364","author":"AH Peden","year":"2004","unstructured":"Peden, A. H., Head, M. W., Ritchie, D. L., Bell, J. E. & Ironside, J. W. Preclinical vCJD after blood transfusion in a PRNP codon 129 heterozygous patient. Lancet \n                           364, 527\u2013529, https:\/\/doi.org\/10.1016\/S0140-6736(04)16811-6 (2004).","journal-title":"Lancet"},{"key":"15778_CR10","doi-asserted-by":"publisher","first-page":"2061","DOI":"10.1016\/S0140-6736(06)69835-8","volume":"368","author":"SJ Wroe","year":"2006","unstructured":"Wroe, S. J. et al. Clinical presentation and pre-mortem diagnosis of variant Creutzfeldt-Jakob disease associated with blood transfusion: a case report. Lancet \n                           368, 2061\u20132067, https:\/\/doi.org\/10.1016\/S0140-6736(06)69835-8 (2006).","journal-title":"Lancet"},{"key":"15778_CR11","doi-asserted-by":"publisher","first-page":"296","DOI":"10.1111\/j.1365-2516.2009.02181.x","volume":"16","author":"A Peden","year":"2010","unstructured":"Peden, A. et al. Variant CJD infection in the spleen of a neurologically asymptomatic UK adult patient with haemophilia. Haemophilia \n                           16, 296\u2013304, https:\/\/doi.org\/10.1111\/j.1365-2516.2009.02181.x (2010).","journal-title":"Haemophilia"},{"key":"15778_CR12","doi-asserted-by":"crossref","unstructured":"Colby, D. W. & Prusiner, S. B. Prions. Cold Spring Harb Perspect Biol \n                           3, a006833, doi:3\/1\/a006833 [pii] 10.1101\/cshperspect.a006833 (2011).","DOI":"10.1101\/cshperspect.a006833"},{"key":"15778_CR13","doi-asserted-by":"crossref","unstructured":"DeArmond, S. J. & Bouzamondo, E. Fundamentals of prion biology and diseases. Toxicology 181\u2013182, 9\u201316, doi:S0300483X02002494 [pii] (2002).","DOI":"10.1016\/S0300-483X(02)00249-4"},{"key":"15778_CR14","doi-asserted-by":"publisher","first-page":"44","DOI":"10.3389\/fcell.2014.00044","volume":"2","author":"L Gasperini","year":"2014","unstructured":"Gasperini, L. & Legname, G. Prion protein and aging. Front Cell Dev Biol \n                           2, 44, https:\/\/doi.org\/10.3389\/fcell.2014.00044 (2014).","journal-title":"Front Cell Dev Biol"},{"key":"15778_CR15","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2164-15-434","volume":"15","author":"M Barbisin","year":"2014","unstructured":"Barbisin, M. et al. Gene expression profiling of brains from bovine spongiform encephalopathy (BSE)-infected cynomolgus macaques. BMC Genomics \n                           15, 434, https:\/\/doi.org\/10.1186\/1471-2164-15-434 (2014).","journal-title":"BMC Genomics"},{"key":"15778_CR16","doi-asserted-by":"publisher","first-page":"2821","DOI":"10.2741\/2275","volume":"12","author":"C Baker","year":"2007","unstructured":"Baker, C., Belbin, O., Kalsheker, N. & Morgan, K. SERPINA3 (aka alpha-1-antichymotrypsin). Front Biosci \n                           12, 2821\u20132835 (2007).","journal-title":"Front Biosci"},{"key":"15778_CR17","doi-asserted-by":"publisher","first-page":"709","DOI":"10.1007\/s00018-005-5077-4","volume":"63","author":"E Miranda","year":"2006","unstructured":"Miranda, E. & Lomas, D. A. Neuroserpin: a serpin to think about. Cell Mol Life Sci \n                           63, 709\u2013722, https:\/\/doi.org\/10.1007\/s00018-005-5077-4 (2006).","journal-title":"Cell Mol Life Sci"},{"key":"15778_CR18","doi-asserted-by":"publisher","first-page":"1821","DOI":"10.1074\/jbc.274.3.1821","volume":"274","author":"SR Hwang","year":"1999","unstructured":"Hwang, S. R., Steineckert, B., Kohn, A., Palkovits, M. & Hook, V. Y. Molecular studies define the primary structure of alpha1-antichymotrypsin (ACT) protease inhibitor in Alzheimer\u2019s disease brains. Comparison of act in hippocampus and liver. J Biol Chem \n                           274, 1821\u20131827 (1999).","journal-title":"J Biol Chem"},{"key":"15778_CR19","doi-asserted-by":"publisher","first-page":"14548","DOI":"10.1074\/jbc.270.24.14548","volume":"270","author":"N Naidoo","year":"1995","unstructured":"Naidoo, N., Cooperman, B. S., Wang, Z. M., Liu, X. Z. & Rubin, H. Identification of lysines within alpha 1-antichymotrypsin important for DNA binding. An unusual combination of DNA-binding elements. J Biol Chem \n                           270, 14548\u201314555 (1995).","journal-title":"J Biol Chem"},{"key":"15778_CR20","doi-asserted-by":"publisher","first-page":"1274","DOI":"10.1110\/ps.9.7.1274","volume":"9","author":"PR Elliott","year":"2000","unstructured":"Elliott, P. R., Pei, X. Y., Dafforn, T. R. & Lomas, D. A. Topography of a 2.0 A structure of alpha1-antitrypsin reveals targets for rational drug design to prevent conformational disease. Protein Sci \n                           9, 1274\u20131281, https:\/\/doi.org\/10.1110\/ps.9.7.1274 (2000).","journal-title":"Protein Sci"},{"key":"15778_CR21","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1136\/thorax.56.1.53","volume":"56","author":"R Mahadeva","year":"2001","unstructured":"Mahadeva, R. et al. Association of alpha(1)-antichymotrypsin deficiency with milder lung disease in patients with cystic fibrosis. Thorax \n                           56, 53\u201358 (2001).","journal-title":"Thorax"},{"key":"15778_CR22","doi-asserted-by":"crossref","first-page":"1110","DOI":"10.1158\/1078-0432.1110.11.3","volume":"11","author":"JM Koomen","year":"2005","unstructured":"Koomen, J. M. et al. Plasma protein profiling for diagnosis of pancreatic cancer reveals the presence of host response proteins. Clin Cancer Res \n                           11, 1110\u20131118 (2005).","journal-title":"Clin Cancer Res"},{"key":"15778_CR23","doi-asserted-by":"crossref","first-page":"2098","DOI":"10.1093\/clinchem\/39.10.2098","volume":"39","author":"J Leinonen","year":"1993","unstructured":"Leinonen, J., Lovgren, T., Vornanen, T. & Stenman, U. H. Double-label time-resolved immunofluorometric assay of prostate-specific antigen and of its complex with alpha 1-antichymotrypsin. Clin Chem \n                           39, 2098\u20132103 (1993).","journal-title":"Clin Chem"},{"key":"15778_CR24","doi-asserted-by":"publisher","first-page":"1368","DOI":"10.1002\/1097-0142(19951015)76:8<1368::AID-CNCR2820760812>3.0.CO;2-N","volume":"76","author":"M Higashiyama","year":"1995","unstructured":"Higashiyama, M. et al. Alpha-1-antichymotrypsin expression in lung adenocarcinoma and its possible association with tumor progression. Cancer \n                           76, 1368\u20131376 (1995).","journal-title":"Cancer"},{"key":"15778_CR25","doi-asserted-by":"publisher","first-page":"887","DOI":"10.1111\/j.1349-7006.2004.tb02198.x","volume":"95","author":"J Yamamura","year":"2004","unstructured":"Yamamura, J. et al. mRNA expression level of estrogen-inducible gene, alpha 1-antichymotrypsin, is a predictor of early tumor recurrence in patients with invasive breast cancers. Cancer Sci \n                           95, 887\u2013892 (2004).","journal-title":"Cancer Sci"},{"key":"15778_CR26","doi-asserted-by":"publisher","first-page":"487","DOI":"10.1016\/0092-8674(88)90462-X","volume":"52","author":"CR Abraham","year":"1988","unstructured":"Abraham, C. R., Selkoe, D. J. & Potter, H. Immunochemical identification of the serine protease inhibitor alpha 1-antichymotrypsin in the brain amyloid deposits of Alzheimer\u2019s disease. Cell \n                           52, 487\u2013501 (1988).","journal-title":"Cell"},{"key":"15778_CR27","doi-asserted-by":"publisher","first-page":"298","DOI":"10.1111\/j.1471-4159.1993.tb03568.x","volume":"61","author":"PE Fraser","year":"1993","unstructured":"Fraser, P. E., Nguyen, J. T., McLachlan, D. R., Abraham, C. R. & Kirschner, D. A. Alpha 1-antichymotrypsin binding to Alzheimer A beta peptides is sequence specific and induces fibril disaggregation in vitro. J Neurochem \n                           61, 298\u2013305 (1993).","journal-title":"J Neurochem"},{"key":"15778_CR28","doi-asserted-by":"publisher","first-page":"28360","DOI":"10.1074\/jbc.273.43.28360","volume":"273","author":"S Janciauskiene","year":"1998","unstructured":"Janciauskiene, S., Rubin, H., Lukacs, C. M. & Wright, H. T. Alzheimer\u2019s peptide Abeta1-42 binds to two beta-sheets of alpha1-antichymotrypsin and transforms it from inhibitor to substrate. J Biol Chem \n                           273, 28360\u201328364 (1998).","journal-title":"J Biol Chem"},{"key":"15778_CR29","doi-asserted-by":"publisher","first-page":"511","DOI":"10.1002\/jnr.10144","volume":"67","author":"YX Sun","year":"2002","unstructured":"Sun, Y. X., Wright, H. T. & Janciauskiene, S. Alpha1-antichymotrypsin\/Alzheimer\u2019s peptide Abeta(1-42) complex perturbs lipid metabolism and activates transcription factors PPARgamma and NFkappaB in human neuroblastoma (Kelly) cells. J Neurosci Res \n                           67, 511\u2013522, https:\/\/doi.org\/10.1002\/jnr.10144 (2002).","journal-title":"J Neurosci Res"},{"key":"15778_CR30","doi-asserted-by":"publisher","first-page":"943","DOI":"10.1007\/s00414-012-0774-7","volume":"126","author":"Q Wang","year":"2012","unstructured":"Wang, Q. et al. Stability of endogenous reference genes in postmortem human brains for normalization of quantitative real-time PCR data: comprehensive evaluation using geNorm, NormFinder, and BestKeeper. Int J Legal Med \n                           126, 943\u2013952, https:\/\/doi.org\/10.1007\/s00414-012-0774-7 (2012).","journal-title":"Int J Legal Med"},{"key":"15778_CR31","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.brainres.2006.09.025","volume":"1123","author":"AD Stan","year":"2006","unstructured":"Stan, A. D. et al. Human postmortem tissue: what quality markers matter? Brain research \n                           1123, 1\u201311, https:\/\/doi.org\/10.1016\/j.brainres.2006.09.025 (2006).","journal-title":"Brain research"},{"issue":"1192\u20131196","key":"15778_CR32","first-page":"1198","volume":"35","author":"O Schoor","year":"2003","unstructured":"Schoor, O. et al. Moderate degradation does not preclude microarray analysis of small amounts of RNA. Biotechniques \n                           35(1192\u20131196), 1198\u20131201 (2003).","journal-title":"Biotechniques"},{"key":"15778_CR33","doi-asserted-by":"publisher","first-page":"573","DOI":"10.1007\/s00414-011-0578-1","volume":"125","author":"A Koppelkamm","year":"2011","unstructured":"Koppelkamm, A., Vennemann, B., Lutz-Bonengel, S., Fracasso, T. & Vennemann, M. RNA integrity in post-mortem samples: influencing parameters and implications on RT-qPCR assays. Int J Legal Med \n                           125, 573\u2013580, https:\/\/doi.org\/10.1007\/s00414-011-0578-1 (2011).","journal-title":"Int J Legal Med"},{"key":"15778_CR34","doi-asserted-by":"publisher","first-page":"126","DOI":"10.1016\/j.mam.2005.12.003","volume":"27","author":"S Fleige","year":"2006","unstructured":"Fleige, S. & Pfaffl, M. W. RNA integrity and the effect on the real-time qRT-PCR performance. Mol Aspects Med \n                           27, 126\u2013139, https:\/\/doi.org\/10.1016\/j.mam.2005.12.003 (2006).","journal-title":"Mol Aspects Med"},{"key":"15778_CR35","doi-asserted-by":"publisher","first-page":"198","DOI":"10.1016\/j.jneumeth.2007.06.001","volume":"165","author":"S Weis","year":"2007","unstructured":"Weis, S. et al. Quality control for microarray analysis of human brain samples: The impact of postmortem factors, RNA characteristics, and histopathology. J Neurosci Methods \n                           165, 198\u2013209, https:\/\/doi.org\/10.1016\/j.jneumeth.2007.06.001 (2007).","journal-title":"J Neurosci Methods"},{"key":"15778_CR36","doi-asserted-by":"publisher","first-page":"5461","DOI":"10.3390\/ijms12095461","volume":"12","author":"I Penna","year":"2011","unstructured":"Penna, I. et al. Selection of candidate housekeeping genes for normalization in human postmortem brain samples. Int J Mol Sci \n                           12, 5461\u20135470, https:\/\/doi.org\/10.3390\/ijms12095461 (2011).","journal-title":"Int J Mol Sci"},{"key":"15778_CR37","doi-asserted-by":"publisher","first-page":"e3870","DOI":"10.1371\/journal.pone.0003870","volume":"3","author":"G Miele","year":"2008","unstructured":"Miele, G. et al. Urinary alpha1-antichymotrypsin: a biomarker of prion infection. PLoS One \n                           3, e3870, https:\/\/doi.org\/10.1371\/journal.pone.0003870 (2008).","journal-title":"PLoS One"},{"key":"15778_CR38","doi-asserted-by":"crossref","first-page":"2383","DOI":"10.1128\/jvi.68.4.2383-2387.1994","volume":"68","author":"IL Campbell","year":"1994","unstructured":"Campbell, I. L., Eddleston, M., Kemper, P., Oldstone, M. B. & Hobbs, M. V. Activation of cerebral cytokine gene expression and its correlation with onset of reactive astrocyte and acute-phase response gene expression in scrapie. J Virol \n                           68, 2383\u20132387 (1994).","journal-title":"J Virol"},{"key":"15778_CR39","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1016\/S0169-328X(00)00028-0","volume":"76","author":"F Dandoy-Dron","year":"2000","unstructured":"Dandoy-Dron, F. et al. Enhanced levels of scrapie responsive gene mRNA in BSE-infected mouse brain. Brain Res Mol Brain Res \n                           76, 173\u2013179 (2000).","journal-title":"Brain Res Mol Brain Res"},{"key":"15778_CR40","doi-asserted-by":"publisher","first-page":"33293","DOI":"10.1074\/jbc.R100016200","volume":"276","author":"GA Silverman","year":"2001","unstructured":"Silverman, G. A. et al. The serpins are an expanding superfamily of structurally similar but functionally diverse proteins. Evolution, mechanism of inhibition, novel functions, and a revised nomenclature. J Biol Chem \n                           276, 33293\u201333296, https:\/\/doi.org\/10.1074\/jbc.R100016200 (2001).","journal-title":"Evolution, mechanism of inhibition, novel functions, and a revised nomenclature. J Biol Chem"},{"key":"15778_CR41","doi-asserted-by":"publisher","first-page":"923","DOI":"10.1038\/35038119","volume":"407","author":"JA Huntington","year":"2000","unstructured":"Huntington, J. A., Read, R. J. & Carrell, R. W. Structure of a serpin-protease complex shows inhibition by deformation. Nature \n                           407, 923\u2013926, https:\/\/doi.org\/10.1038\/35038119 (2000).","journal-title":"Nature"},{"key":"15778_CR42","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1016\/0197-4580(90)90045-2","volume":"11","author":"CR Abraham","year":"1990","unstructured":"Abraham, C. R., Shirahama, T. & Potter, H. Alpha 1-antichymotrypsin is associated solely with amyloid deposits containing the beta-protein. Amyloid and cell localization of alpha 1-antichymotrypsin. Neurobiol Aging \n                           11, 123\u2013129 (1990).","journal-title":"Neurobiol Aging"},{"key":"15778_CR43","doi-asserted-by":"publisher","first-page":"715","DOI":"10.1016\/0306-4522(89)90292-3","volume":"32","author":"CR Abraham","year":"1989","unstructured":"Abraham, C. R., Selkoe, D. J., Potter, H., Price, D. L. & Cork, L. C. Alpha 1-antichymotrypsin is present together with the beta-protein in monkey brain amyloid deposits. Neuroscience \n                           32, 715\u2013720 (1989).","journal-title":"Neuroscience"},{"key":"15778_CR44","doi-asserted-by":"publisher","first-page":"200","DOI":"10.1007\/BF00294446","volume":"82","author":"JM Rozemuller","year":"1991","unstructured":"Rozemuller, J. M. et al. Distribution pattern and functional state of alpha 1-antichymotrypsin in plaques and vascular amyloid in Alzheimer\u2019s disease. A immunohistochemical study with monoclonal antibodies against native and inactivated alpha 1-antichymotrypsin. Acta Neuropathol \n                           82, 200\u2013207 (1991).","journal-title":"Acta Neuropathol"},{"key":"15778_CR45","doi-asserted-by":"publisher","first-page":"294","DOI":"10.1016\/0304-3940(89)90636-8","volume":"105","author":"L Verga","year":"1989","unstructured":"Verga, L. et al. Alzheimer patients and Down patients: cerebral preamyloid deposits differ ultrastructurally and histochemically from the amyloid of senile plaques. Neurosci Lett \n                           105, 294\u2013299 (1989).","journal-title":"Neurosci Lett"},{"key":"15778_CR46","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1097\/00001756-199202000-00020","volume":"3","author":"PA Gollin","year":"1992","unstructured":"Gollin, P. A., Kalaria, R. N., Eikelenboom, P., Rozemuller, A. & Perry, G. Alpha 1-antitrypsin and alpha 1-antichymotrypsin are in the lesions of Alzheimer\u2019s disease. Neuroreport \n                           3, 201\u2013203 (1992).","journal-title":"Neuroreport"},{"key":"15778_CR47","doi-asserted-by":"publisher","first-page":"2003","DOI":"10.1016\/S0002-9440(10)64839-0","volume":"157","author":"L Mucke","year":"2000","unstructured":"Mucke, L. et al. Astroglial expression of human alpha(1)-antichymotrypsin enhances alzheimer-like pathology in amyloid protein precursor transgenic mice. Am J Pathol \n                           157, 2003\u20132010 (2000).","journal-title":"Am J Pathol"},{"key":"15778_CR48","doi-asserted-by":"crossref","first-page":"1444","DOI":"10.1523\/JNEUROSCI.21-05-01444.2001","volume":"21","author":"LN Nilsson","year":"2001","unstructured":"Nilsson, L. N. et al. Alpha-1-antichymotrypsin promotes beta-sheet amyloid plaque deposition in a transgenic mouse model of Alzheimer\u2019s disease. J Neurosci \n                           21, 1444\u20131451 (2001).","journal-title":"J Neurosci"},{"key":"15778_CR49","doi-asserted-by":"crossref","unstructured":"Salvatore, M. et al. Alpha1 antichymotrypsin signal peptide polymorphism in sporadic Creutzfeldt-Jakob disease. Neurosci Lett \n                           227, 140-142, doi:S030439409700308X [pii] (1997).","DOI":"10.1016\/S0304-3940(97)00308-X"},{"key":"15778_CR50","doi-asserted-by":"publisher","first-page":"242","DOI":"10.1016\/j.bbrc.2010.01.110","volume":"393","author":"F Zsila","year":"2010","unstructured":"Zsila, F. Inhibition of heat- and chemical-induced aggregation of various proteins reveals chaperone-like activity of the acute-phase component and serine protease inhibitor human alpha(1)-antitrypsin. Biochem Biophys Res Commun \n                           393, 242\u2013247, https:\/\/doi.org\/10.1016\/j.bbrc.2010.01.110 (2010).","journal-title":"Biochem Biophys Res Commun"},{"key":"15778_CR51","doi-asserted-by":"publisher","first-page":"383","DOI":"10.4161\/pri.26416","volume":"7","author":"F Llorens","year":"2013","unstructured":"Llorens, F. et al. PrP mRNA and protein expression in brain and PrP(c) in CSF in Creutzfeldt-Jakob disease MM1 and VV2. Prion \n                           7, 383\u2013393, https:\/\/doi.org\/10.4161\/pri.26416 (2013).","journal-title":"Prion"},{"key":"15778_CR52","doi-asserted-by":"publisher","first-page":"818","DOI":"10.1053\/j.gastro.2012.12.029","volume":"144","author":"M Santamaria","year":"2013","unstructured":"Santamaria, M. et al. Nuclear alpha1-antichymotrypsin promotes chromatin condensation and inhibits proliferation of human hepatocellular carcinoma cells. Gastroenterology \n                           144, 818\u2013828 e814, https:\/\/doi.org\/10.1053\/j.gastro.2012.12.029 (2013).","journal-title":"Gastroenterology"},{"key":"15778_CR53","doi-asserted-by":"publisher","first-page":"2411","DOI":"10.1242\/jcs.01094","volume":"117","author":"A Mange","year":"2004","unstructured":"Mange, A., Crozet, C., Lehmann, S. & Beranger, F. Scrapie-like prion protein is translocated to the nuclei of infected cells independently of proteasome inhibition and interacts with chromatin. J Cell Sci \n                           117, 2411\u20132416, https:\/\/doi.org\/10.1242\/jcs.01094 (2004).","journal-title":"J Cell Sci"},{"key":"15778_CR54","doi-asserted-by":"publisher","first-page":"389","DOI":"10.1517\/17460441.2015.1016498","volume":"10","author":"ML Bolognesi","year":"2015","unstructured":"Bolognesi, M. L. & Legname, G. Approaches for discovering anti-prion compounds: lessons learned and challenges ahead. Expert opinion on drug discovery \n                           10, 389\u2013397, https:\/\/doi.org\/10.1517\/17460441.2015.1016498 (2015).","journal-title":"Expert opinion on drug discovery"},{"key":"15778_CR55","doi-asserted-by":"publisher","first-page":"370ra183","DOI":"10.1126\/scitranslmed.aaf6188","volume":"8","author":"L Concha-Marambio","year":"2016","unstructured":"Concha-Marambio, L. et al. Detection of prions in blood from patients with variant Creutzfeldt-Jakob disease. Sci Transl Med \n                           8, 370ra183, https:\/\/doi.org\/10.1126\/scitranslmed.aaf6188 (2016).","journal-title":"Sci Transl Med"},{"key":"15778_CR56","doi-asserted-by":"publisher","first-page":"370ra182","DOI":"10.1126\/scitranslmed.aag1257","volume":"8","author":"D Bougard","year":"2016","unstructured":"Bougard, D. et al. Detection of prions in the plasma of presymptomatic and symptomatic patients with variant Creutzfeldt-Jakob disease. Sci Transl Med \n                           8, 370ra182, https:\/\/doi.org\/10.1126\/scitranslmed.aag1257 (2016).","journal-title":"Sci Transl Med"},{"key":"15778_CR57","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1001\/jamaneurol.2016.4614","volume":"74","author":"M Bongianni","year":"2017","unstructured":"Bongianni, M. et al. Diagnosis of Human Prion Disease Using Real-Time Quaking-Induced Conversion Testing of Olfactory Mucosa and Cerebrospinal Fluid Samples. JAMA Neurol \n                           74, 155\u2013162, https:\/\/doi.org\/10.1001\/jamaneurol.2016.4614 (2017).","journal-title":"JAMA Neurol"},{"key":"15778_CR58","doi-asserted-by":"publisher","first-page":"402","DOI":"10.1006\/meth.2001.1262","volume":"25","author":"KJ Livak","year":"2001","unstructured":"Livak, K. J. & Schmittgen, T. D. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods \n                           25, 402\u2013408, https:\/\/doi.org\/10.1006\/meth.2001.1262 (2001).","journal-title":"Methods"},{"key":"15778_CR59","doi-asserted-by":"publisher","first-page":"413","DOI":"10.3892\/ol.2011.280","volume":"2","author":"J Dimberg","year":"2011","unstructured":"Dimberg, J. et al. Expression of the serine protease inhibitor serpinA3 in human colorectal adenocarcinomas. Oncol Lett \n                           2, 413\u2013418, https:\/\/doi.org\/10.3892\/ol.2011.280 (2011).","journal-title":"Oncol Lett"},{"key":"15778_CR60","doi-asserted-by":"publisher","first-page":"2173","DOI":"10.2147\/OTT.S133022","volume":"10","author":"D Luo","year":"2017","unstructured":"Luo, D. et al. Serpin peptidase inhibitor, clade A member 3 (SERPINA3), is overexpressed in glioma and associated with poor prognosis in glioma patients. Onco Targets Ther \n                           10, 2173\u20132181, https:\/\/doi.org\/10.2147\/OTT.S133022 (2017).","journal-title":"Onco Targets Ther"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-15778-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-15778-8","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-15778-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,23]],"date-time":"2022-12-23T13:41:39Z","timestamp":1671802899000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-15778-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,11,15]]},"references-count":60,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2017,12]]}},"alternative-id":["15778"],"URL":"https:\/\/doi.org\/10.1038\/s41598-017-15778-8","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,11,15]]},"assertion":[{"value":"30 August 2017","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 November 2017","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 November 2017","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare that they have no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}],"article-number":"15637"}}