{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T11:50:25Z","timestamp":1789386625731,"version":"build-2803163510"},"reference-count":69,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2017,9,4]],"date-time":"2017-09-04T00:00:00Z","timestamp":1504483200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2017,9,4]],"date-time":"2017-09-04T00:00:00Z","timestamp":1504483200000},"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>Human immunodeficiency virus type-1 (HIV-1)-associated neurocognitive disorder (HAND) remains an important neurological manifestation that adversely affects a patient\u2019s quality of life. HIV-1 matrix protein p17 (p17) has been detected in autoptic brain tissue of HAND individuals who presented early with severe AIDS encephalopathy. We hypothesised that the ability of p17 to misfold may result in the generation of toxic assemblies in the brain and may be relevant for HAND pathogenesis. A multidisciplinary integrated approach has been applied to determine the ability of p17 to form soluble amyloidogenic assemblies <jats:italic>in vitro<\/jats:italic>. To provide new information into the potential pathogenic role of soluble p17 species in HAND, their toxicological capability was evaluated <jats:italic>in vivo<\/jats:italic>. In <jats:italic>C<\/jats:italic>. <jats:italic>elegans<\/jats:italic>, capable of recognising toxic assemblies of amyloidogenic proteins, p17 induces a specific toxic effect which can be counteracted by tetracyclines, drugs able to hinder the formation of large oligomers and consequently amyloid fibrils. The intrahippocampal injection of p17 in mice reduces their cognitive function and induces behavioral deficiencies. These findings offer a new way of thinking about the possible cause of neurodegeneration in HIV-1-seropositive patients, which engages the ability of p17 to form soluble toxic assemblies.<\/jats:p>","DOI":"10.1038\/s41598-017-10875-0","type":"journal-article","created":{"date-parts":[[2017,8,29]],"date-time":"2017-08-29T09:55:42Z","timestamp":1504000542000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["HIV-1 matrix protein p17 misfolding forms toxic amyloidogenic assemblies that induce neurocognitive disorders"],"prefix":"10.1038","volume":"7","author":[{"given":"Yasmin","family":"Zeinolabediny","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Caccuri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Colombo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federica","family":"Morelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margherita","family":"Romeo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Rossi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Schiarea","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2246-0772","authenticated-orcid":false,"given":"Carlotta","family":"Ciaramelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3670-6262","authenticated-orcid":false,"given":"Cristina","family":"Airoldi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ria","family":"Weston","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liu","family":"Donghui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jerzy","family":"Krupinski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rub\u00e9n","family":"Corpas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"Garc\u00eda-Lara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Sarroca","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Coral","family":"Sanfeliu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Slevin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arnaldo","family":"Caruso","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario","family":"Salmona","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2258-0531","authenticated-orcid":false,"given":"Luisa","family":"Diomede","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,9,4]]},"reference":[{"key":"10875_CR1","first-page":"54","volume":"17","author":"D Elbirt","year":"2015","unstructured":"Elbirt, D. et al. HIV-associated neurocognitive disorders (HAND). Isr Med Assoc J \n                           17, 54\u201359 (2015).","journal-title":"Isr Med Assoc J"},{"key":"10875_CR2","first-page":"45","volume":"18","author":"SL Letendre","year":"2010","unstructured":"Letendre, S. L., Ellis, R. J., Ances, B. M. & McCutchan, J. A. Neurologic complications of HIV disease and their treatment. Top HIV Med \n                           18, 45\u201355 (2010).","journal-title":"Top HIV Med"},{"key":"10875_CR3","doi-asserted-by":"publisher","first-page":"2251","DOI":"10.1097\/QAD.0000000000000400","volume":"28","author":"V Dahl","year":"2014","unstructured":"Dahl, V. et al. Low levels of HIV-1 RNA detected in the cerebrospinal fluid after up to 10 years of suppressive therapy are associated with local immune activation. AIDS \n                           28, 2251\u20132258, doi:10.1097\/QAD.0000000000000400 (2014).","journal-title":"AIDS"},{"key":"10875_CR4","doi-asserted-by":"crossref","first-page":"2928","DOI":"10.1128\/jvi.71.4.2928-2933.1997","volume":"71","author":"I Teo","year":"1997","unstructured":"Teo, I. et al. Circular forms of unintegrated human immunodeficiency virus type 1 DNA and high levels of viral protein expression: association with dementia and multinucleated giant cells in the brains of patients with AIDS. J Virol \n                           71, 2928\u20132933 (1997).","journal-title":"J Virol"},{"key":"10875_CR5","doi-asserted-by":"publisher","first-page":"1415","DOI":"10.1212\/WNL.0b013e31828c2e9e","volume":"80","author":"P Desplats","year":"2013","unstructured":"Desplats, P. et al. Molecular and pathologic insights from latent HIV-1 infection in the human brain. Neurology \n                           80, 1415\u20131423, doi:10.1212\/WNL.0b013e31828c2e9e (2013).","journal-title":"Neurology"},{"key":"10875_CR6","doi-asserted-by":"publisher","unstructured":"Eggers, C. et al. HIV-1-associated neurocognitive disorder: epidemiology, pathogenesis, diagnosis, and treatment. J Neurol, doi:10.1007\/s00415-017-8503-2 (2017).","DOI":"10.1007\/s00415-017-8503-2"},{"key":"10875_CR7","doi-asserted-by":"publisher","first-page":"1120","DOI":"10.1111\/j.1460-9568.2006.04646.x","volume":"23","author":"A Kasyanov","year":"2006","unstructured":"Kasyanov, A., Tamamura, H., Fujii, N. & Xiong, H. HIV-1 gp120 enhances giant depolarizing potentials via chemokine receptor CXCR4 in neonatal rat hippocampus. Eur J Neurosci \n                           23, 1120\u20131128, doi:10.1111\/j.1460-9568.2006.04646.x (2006).","journal-title":"Eur J Neurosci"},{"key":"10875_CR8","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0023915","volume":"6","author":"SM Lu","year":"2011","unstructured":"Lu, S. M. et al. HIV-1 Tat-induced microgliosis and synaptic damage via interactions between peripheral and central myeloid cells. PLoS One \n                           6, e23915, doi:10.1371\/journal.pone.0023915 (2011).","journal-title":"PLoS One"},{"key":"10875_CR9","doi-asserted-by":"publisher","first-page":"319","DOI":"10.1007\/s11481-011-9310-7","volume":"7","author":"C Power","year":"2012","unstructured":"Power, C., Hui, E., Vivithanaporn, P., Acharjee, S. & Polyak, M. Delineating HIV-associated neurocognitive disorders using transgenic models: the neuropathogenic actions of Vpr. J Neuroimmune Pharmacol \n                           7, 319\u2013331, doi:10.1007\/s11481-011-9310-7 (2012).","journal-title":"J Neuroimmune Pharmacol"},{"key":"10875_CR10","doi-asserted-by":"publisher","first-page":"212","DOI":"10.1016\/j.mvr.2008.11.003","volume":"77","author":"B Yang","year":"2009","unstructured":"Yang, B., Akhter, S., Chaudhuri, A. & Kanmogne, G. D. HIV-1 gp120 induces cytokine expression, leukocyte adhesion, and transmigration across the blood-brain barrier: modulatory effects of STAT1 signaling. Microvasc Res \n                           77, 212\u2013219, doi:10.1016\/j.mvr.2008.11.003 (2009).","journal-title":"Microvasc Res"},{"key":"10875_CR11","doi-asserted-by":"publisher","first-page":"3867","DOI":"10.1073\/pnas.0800370105","volume":"105","author":"S Fiorentini","year":"2008","unstructured":"Fiorentini, S. et al. HIV-1 matrix protein p17 induces human plasmacytoid dendritic cells to acquire a migratory immature cell phenotype. Proc Natl Acad Sci USA \n                           105, 3867\u20133872, doi:10.1073\/pnas.0800370105 (2008).","journal-title":"Proc Natl Acad Sci USA"},{"key":"10875_CR12","first-page":"1","volume":"29","author":"S Fiorentini","year":"2006","unstructured":"Fiorentini, S., Marini, E., Caracciolo, S. & Caruso, A. Functions of the HIV-1 matrix protein p17. New Microbiol \n                           29, 1\u201310 (2006).","journal-title":"New Microbiol"},{"key":"10875_CR13","doi-asserted-by":"publisher","first-page":"14580","DOI":"10.1073\/pnas.1206605109","volume":"109","author":"F Caccuri","year":"2012","unstructured":"Caccuri, F. et al. HIV-1 matrix protein p17 promotes angiogenesis via chemokine receptors CXCR1 and CXCR2. Proc Natl Acad Sci USA \n                           109, 14580\u201314585, doi:10.1073\/pnas.1206605109 (2012).","journal-title":"Proc Natl Acad Sci USA"},{"key":"10875_CR14","doi-asserted-by":"publisher","first-page":"1403","DOI":"10.1182\/blood-2015-11-681411","volume":"127","author":"R Dolcetti","year":"2016","unstructured":"Dolcetti, R., Gloghini, A., Caruso, A. & Carbone, A. A lymphomagenic role for HIV beyond immune suppression? Blood \n                           127, 1403\u20131409, doi:10.1182\/blood-2015-11-681411 (2016).","journal-title":"Blood"},{"key":"10875_CR15","doi-asserted-by":"publisher","first-page":"14807","DOI":"10.1073\/pnas.0506857102","volume":"102","author":"M Popovic","year":"2005","unstructured":"Popovic, M. et al. Persistence of HIV-1 structural proteins and glycoproteins in lymph nodes of patients under highly active antiretroviral therapy. Proc Natl Acad Sci USA \n                           102, 14807\u201314812, doi:10.1073\/pnas.0506857102 (2005).","journal-title":"Proc Natl Acad Sci USA"},{"key":"10875_CR16","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0006093","volume":"4","author":"S Reuse","year":"2009","unstructured":"Reuse, S. et al. Synergistic activation of HIV-1 expression by deacetylase inhibitors and prostratin: implications for treatment of latent infection. PLoS One \n                           4, e6093, doi:10.1371\/journal.pone.0006093 (2009).","journal-title":"PLoS One"},{"key":"10875_CR17","doi-asserted-by":"publisher","first-page":"1738","DOI":"10.1016\/j.bcp.2007.02.011","volume":"73","author":"C Vandergeeten","year":"2007","unstructured":"Vandergeeten, C. et al. HIV-1 protease inhibitors do not interfere with provirus transcription and host cell apoptosis induced by combined treatment TNF-alpha+ TSA. Biochem Pharmacol \n                           73, 1738\u20131748, doi:10.1016\/j.bcp.2007.02.011 (2007).","journal-title":"Biochem Pharmacol"},{"key":"10875_CR18","doi-asserted-by":"publisher","first-page":"433","DOI":"10.1016\/j.pharmthera.2010.08.005","volume":"128","author":"S Fiorentini","year":"2010","unstructured":"Fiorentini, S., Giagulli, C., Caccuri, F., Magiera, A. K. & Caruso, A. HIV-1 matrix protein p17: a candidate antigen for therapeutic vaccines against AIDS. Pharmacol Ther \n                           128, 433\u2013444, doi:10.1016\/j.pharmthera.2010.08.005 (2010).","journal-title":"Pharmacol Ther"},{"key":"10875_CR19","doi-asserted-by":"publisher","first-page":"5706","DOI":"10.1128\/JVI.03142-13","volume":"88","author":"F Caccuri","year":"2014","unstructured":"Caccuri, F. et al. Simian immunodeficiency virus and human immunodeficiency virus type 1 matrix proteins specify different capabilities to modulate B cell growth. J Virol \n                           88, 5706\u20135717, doi:10.1128\/JVI.03142-13 (2014).","journal-title":"J Virol"},{"key":"10875_CR20","doi-asserted-by":"publisher","first-page":"2274","DOI":"10.1182\/blood-2011-06-364083","volume":"119","author":"C Giagulli","year":"2012","unstructured":"Giagulli, C. et al. HIV-1 matrix protein p17 binds to the IL-8 receptor CXCR1 and shows IL-8-like chemokine activity on monocytes through Rho\/ROCK activation. Blood \n                           119, 2274\u20132283, doi:10.1182\/blood-2011-06-364083 (2012).","journal-title":"Blood"},{"key":"10875_CR21","doi-asserted-by":"publisher","first-page":"846","DOI":"10.1161\/ATVBAHA.113.302478","volume":"34","author":"F Caccuri","year":"2014","unstructured":"Caccuri, F. et al. HIV-1 matrix protein p17 promotes lymphangiogenesis and activates the endothelin-1\/endothelin B receptor axis. Arterioscler Thromb Vasc Biol \n                           34, 846\u2013856, doi:10.1161\/ATVBAHA.113.302478 (2014).","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"10875_CR22","doi-asserted-by":"publisher","first-page":"19541","DOI":"10.1074\/jbc.M110.191270","volume":"286","author":"MA De Francesco","year":"2011","unstructured":"De Francesco, M. A., Baronio, M. & Poiesi, C. HIV-1 p17 matrix protein interacts with heparan sulfate side chain of CD44v3, syndecan-2, and syndecan-4 proteoglycans expressed on human activated CD4+ T cells affecting tumor necrosis factor alpha and interleukin 2 production. J Biol Chem \n                           286, 19541\u201319548, doi:10.1074\/jbc.M110.191270 (2011).","journal-title":"J Biol Chem"},{"key":"10875_CR23","doi-asserted-by":"publisher","first-page":"1150","DOI":"10.1074\/jbc.M112.400077","volume":"288","author":"A Bugatti","year":"2013","unstructured":"Bugatti, A. et al. Molecular interaction studies of HIV-1 matrix protein p17 and heparin: identification of the heparin-binding motif of p17 as a target for the development of multitarget antagonists. J Biol Chem \n                           288, 1150\u20131161, doi:10.1074\/jbc.M112.400077 (2013).","journal-title":"J Biol Chem"},{"key":"10875_CR24","doi-asserted-by":"publisher","first-page":"1072","DOI":"10.1016\/j.vaccine.2013.12.051","volume":"32","author":"ML Iaria","year":"2014","unstructured":"Iaria, M. L. et al. Synthetic HIV-1 matrix protein p17-based AT20-KLH therapeutic immunization in HIV-1-infected patients receiving antiretroviral treatment: A phase I safety and immunogenicity study. Vaccine \n                           32, 1072\u20131078, doi:10.1016\/j.vaccine.2013.12.051 (2014).","journal-title":"Vaccine"},{"key":"10875_CR25","doi-asserted-by":"publisher","first-page":"614","DOI":"10.1007\/s12035-012-8320-7","volume":"46","author":"G De Chiara","year":"2012","unstructured":"De Chiara, G. et al. Infectious agents and neurodegeneration. Mol Neurobiol \n                           46, 614\u2013638, doi:10.1007\/s12035-012-8320-7 (2012).","journal-title":"Mol Neurobiol"},{"key":"10875_CR26","doi-asserted-by":"publisher","first-page":"3099","DOI":"10.1073\/pnas.93.7.3099","volume":"93","author":"CP Hill","year":"1996","unstructured":"Hill, C. P., Worthylake, D., Bancroft, D. P., Christensen, A. M. & Sundquist, W. I. Crystal structures of the trimeric human immunodeficiency virus type 1 matrix protein: implications for membrane association and assembly. Proc Natl Acad Sci USA \n                           93, 3099\u20133104 (1996).","journal-title":"Proc Natl Acad Sci USA"},{"key":"10875_CR27","doi-asserted-by":"publisher","first-page":"198","DOI":"10.1006\/jmbi.1994.1719","volume":"244","author":"MA Massiah","year":"1994","unstructured":"Massiah, M. A. et al. Three-dimensional structure of the human immunodeficiency virus type 1 matrix protein. J Mol Biol \n                           244, 198\u2013223, doi:10.1006\/jmbi.1994.1719 (1994).","journal-title":"J Mol Biol"},{"key":"10875_CR28","doi-asserted-by":"publisher","DOI":"10.1186\/1742-4690-2-18","volume":"2","author":"RS Doherty","year":"2005","unstructured":"Doherty, R. S. et al. BioAfrica\u2019s HIV-1 proteomics resource: combining protein data with bioinformatics tools. Retrovirology \n                           2, 18, doi:10.1186\/1742-4690-2-18 (2005).","journal-title":"Retrovirology"},{"key":"10875_CR29","doi-asserted-by":"publisher","first-page":"12196","DOI":"10.1128\/JVI.01197-09","volume":"83","author":"A Alfadhli","year":"2009","unstructured":"Alfadhli, A., Still, A. & Barklis, E. Analysis of human immunodeficiency virus type 1 matrix binding to membranes and nucleic acids. J Virol \n                           83, 12196\u201312203, doi:10.1128\/JVI.01197-09 (2009).","journal-title":"J Virol"},{"key":"10875_CR30","doi-asserted-by":"publisher","first-page":"11364","DOI":"10.1073\/pnas.0602818103","volume":"103","author":"JS Saad","year":"2006","unstructured":"Saad, J. S. et al. Structural basis for targeting HIV-1 Gag proteins to the plasma membrane for virus assembly. Proc Natl Acad Sci USA \n                           103, 11364\u201311369, doi:10.1073\/pnas.0602818103 (2006).","journal-title":"Proc Natl Acad Sci USA"},{"key":"10875_CR31","doi-asserted-by":"publisher","first-page":"487","DOI":"10.1038\/ncb0604-487","volume":"6","author":"MA De Matteis","year":"2004","unstructured":"De Matteis, M. A. & Godi, A. PI-loting membrane traffic. Nat Cell Biol \n                           6, 487\u2013492, doi:10.1038\/ncb0604-487 (2004).","journal-title":"Nat Cell Biol"},{"key":"10875_CR32","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1016\/j.jmgm.2006.09.009","volume":"26","author":"H Verli","year":"2007","unstructured":"Verli, H., Calazans, A., Brindeiro, R., Tanuri, A. & Guimaraes, J. A. Molecular dynamics analysis of HIV-1 matrix protein: clarifying differences between crystallographic and solution structures. J Mol Graph Model \n                           26, 62\u201368, doi:10.1016\/j.jmgm.2006.09.009 (2007).","journal-title":"J Mol Graph Model"},{"key":"10875_CR33","doi-asserted-by":"publisher","first-page":"611","DOI":"10.1007\/BF00294238","volume":"79","author":"H Budka","year":"1990","unstructured":"Budka, H. Human immunodeficiency virus (HIV) envelope and core proteins in CNS tissues of patients with the acquired immune deficiency syndrome (AIDS). Acta Neuropathol \n                           79, 611\u2013619 (1990).","journal-title":"Acta Neuropathol"},{"key":"10875_CR34","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1111\/j.1365-2990.1991.tb00707.x","volume":"17","author":"C Geny","year":"1991","unstructured":"Geny, C. et al. Multifocal multinucleated giant cell myelitis in an AIDS patient. Neuropathol Appl Neurobiol \n                           17, 157\u2013162 (1991).","journal-title":"Neuropathol Appl Neurobiol"},{"key":"10875_CR35","first-page":"37","volume":"149","author":"C Lacroix","year":"1993","unstructured":"Lacroix, C., Vazeux, R., Brousse, N., Blanche, S. & Tardieu, M. [A neuropathological study of 10 HIV-infected children]. Rev Neurol (Paris) \n                           149, 37\u201345 (1993).","journal-title":"Rev Neurol (Paris)"},{"key":"10875_CR36","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1002\/(SICI)1097-010X(19990701)284:2<147::AID-JEZ4>3.0.CO;2-Z","volume":"284","author":"D Jones","year":"1999","unstructured":"Jones, D. & Candido, E. P. Feeding is inhibited by sublethal concentrations of toxicants and by heat stress in the nematode Caenorhabditis elegans: relationship to the cellular stress response. J Exp Zool \n                           284, 147\u2013157 (1999).","journal-title":"J Exp Zool"},{"key":"10875_CR37","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1016\/j.ab.2010.12.032","volume":"411","author":"M Beeg","year":"2011","unstructured":"Beeg, M., Stravalaci, M., Bastone, A., Salmona, M. & Gobbi, M. A modified protocol to prepare seed-free starting solutions of amyloid-beta (Abeta)(1)(\u2212)(4)(0) and Abeta(1)(\u2212)(4)(2) from the corresponding depsipeptides. Anal Biochem \n                           411, 297\u2013299, doi:10.1016\/j.ab.2010.12.032 (2011).","journal-title":"Anal Biochem"},{"key":"10875_CR38","doi-asserted-by":"publisher","first-page":"3543","DOI":"10.1182\/blood-2013-10-525634","volume":"123","author":"L Diomede","year":"2014","unstructured":"Diomede, L. et al. A Caenorhabditis elegans-based assay recognizes immunoglobulin light chains causing heart amyloidosis. Blood \n                           123, 3543\u20133552, doi:10.1182\/blood-2013-10-525634 (2014).","journal-title":"Blood"},{"key":"10875_CR39","doi-asserted-by":"publisher","first-page":"27796","DOI":"10.1074\/jbc.M111.334979","volume":"287","author":"M Stravalaci","year":"2012","unstructured":"Stravalaci, M. et al. Specific recognition of biologically active amyloid-beta oligomers by a new surface plasmon resonance-based immunoassay and an in vivo assay in Caenorhabditis elegans. J Biol Chem \n                           287, 27796\u201327805, doi:10.1074\/jbc.M111.334979 (2012).","journal-title":"J Biol Chem"},{"key":"10875_CR40","doi-asserted-by":"publisher","unstructured":"Diomede, L. et al. Cardiac light chain amyloidosis: The role of metal ions in oxidative stress and mitochondrial damage. Antioxidants & redox signaling, doi:10.1089\/ars.2016.6848 (2017).","DOI":"10.1089\/ars.2016.6848"},{"key":"10875_CR41","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0017831","volume":"6","author":"C Giagulli","year":"2011","unstructured":"Giagulli, C. et al. Opposite effects of HIV-1 p17 variants on PTEN activation and cell growth in B cells. PLoS One \n                           6, e17831, doi:10.1371\/journal.pone.0017831 (2011).","journal-title":"PLoS One"},{"key":"10875_CR42","doi-asserted-by":"publisher","first-page":"24143","DOI":"10.1074\/jbc.M114.576256","volume":"289","author":"M Messa","year":"2014","unstructured":"Messa, M. et al. The peculiar role of the A2V mutation in amyloid-beta (Abeta) 1\u201342 molecular assembly. J Biol Chem \n                           289, 24143\u201324152, doi:10.1074\/jbc.M114.576256 (2014).","journal-title":"J Biol Chem"},{"key":"10875_CR43","doi-asserted-by":"publisher","first-page":"14331","DOI":"10.1073\/pnas.1514748112","volume":"112","author":"R Dolcetti","year":"2015","unstructured":"Dolcetti, R. et al. Role of HIV-1 matrix protein p17 variants in lymphoma pathogenesis. Proc Natl Acad Sci USA \n                           112, 14331\u201314336, doi:10.1073\/pnas.1514748112 (2015).","journal-title":"Proc Natl Acad Sci USA"},{"key":"10875_CR44","doi-asserted-by":"publisher","first-page":"11587","DOI":"10.1073\/pnas.0404649101","volume":"101","author":"Z Wu","year":"2004","unstructured":"Wu, Z. et al. Total chemical synthesis of N-myristoylated HIV-1 matrix protein p17: structural and mechanistic implications of p17 myristoylation. Proc Natl Acad Sci USA \n                           101, 11587\u201311592, doi:10.1073\/pnas.0404649101 (2004).","journal-title":"Proc Natl Acad Sci USA"},{"key":"10875_CR45","doi-asserted-by":"publisher","first-page":"5987","DOI":"10.1021\/jm400161p","volume":"56","author":"T Stoilova","year":"2013","unstructured":"Stoilova, T., Colombo, L., Forloni, G., Tagliavini, F. & Salmona, M. A new face for old antibiotics: tetracyclines in treatment of amyloidoses. J Med Chem \n                           56, 5987\u20136006, doi:10.1021\/jm400161p (2013).","journal-title":"J Med Chem"},{"key":"10875_CR46","doi-asserted-by":"publisher","first-page":"4013","DOI":"10.1073\/pnas.1402228111","volume":"111","author":"KE Matlack","year":"2014","unstructured":"Matlack, K. E. et al. Clioquinol promotes the degradation of metal-dependent amyloid-beta (Abeta) oligomers to restore endocytosis and ameliorate Abeta toxicity. Proc Natl Acad Sci USA \n                           111, 4013\u20134018, doi:10.1073\/pnas.1402228111 (2014).","journal-title":"Proc Natl Acad Sci USA"},{"key":"10875_CR47","doi-asserted-by":"publisher","first-page":"463","DOI":"10.1039\/C0OB00303D","volume":"9","author":"C Airoldi","year":"2011","unstructured":"Airoldi, C. et al. Tetracycline prevents Abeta oligomer toxicity through an atypical supramolecular interaction. Org Biomol Chem \n                           9, 463\u2013472, doi:10.1039\/c0ob00303d (2011).","journal-title":"Org Biomol Chem"},{"key":"10875_CR48","doi-asserted-by":"publisher","first-page":"18383","DOI":"10.1002\/chem.201503086","volume":"21","author":"M Bonanomi","year":"2015","unstructured":"Bonanomi, M. et al. How Epigallocatechin-3-gallate and Tetracycline Interact with the Josephin Domain of Ataxin-3 and Alter Its Aggregation Mode. Chemistry \n                           21, 18383\u201318393, doi:10.1002\/chem.201503086 (2015).","journal-title":"Chemistry"},{"key":"10875_CR49","doi-asserted-by":"publisher","first-page":"404","DOI":"10.1016\/S0014-5793(00)02380-2","volume":"487","author":"G Forloni","year":"2001","unstructured":"Forloni, G., Colombo, L., Girola, L., Tagliavini, F. & Salmona, M. Anti-amyloidogenic activity of tetracyclines: studies in vitro. FEBS Lett \n                           487, 404\u2013407 (2001).","journal-title":"FEBS Lett"},{"key":"10875_CR50","doi-asserted-by":"crossref","first-page":"3474","DOI":"10.1128\/jvi.71.5.3474-3483.1997","volume":"71","author":"PM Cannon","year":"1997","unstructured":"Cannon, P. M. et al. Structure-function studies of the human immunodeficiency virus type 1 matrix protein, p17. J Virol \n                           71, 3474\u20133483 (1997).","journal-title":"J Virol"},{"key":"10875_CR51","doi-asserted-by":"publisher","first-page":"2106","DOI":"10.1111\/j.1582-4934.2010.01239.x","volume":"15","author":"M Zampagni","year":"2011","unstructured":"Zampagni, M. et al. A comparison of the biochemical modifications caused by toxic and non-toxic protein oligomers in cells. J Cell Mol Med \n                           15, 2106\u20132116, doi:10.1111\/j.1582-4934.2010.01239.x (2011).","journal-title":"J Cell Mol Med"},{"key":"10875_CR52","doi-asserted-by":"publisher","first-page":"2309","DOI":"10.1021\/cb500505m","volume":"9","author":"B Mannini","year":"2014","unstructured":"Mannini, B. et al. Toxicity of protein oligomers is rationalized by a function combining size and surface hydrophobicity. ACS Chem Biol \n                           9, 2309\u20132317, doi:10.1021\/cb500505m (2014).","journal-title":"ACS Chem Biol"},{"key":"10875_CR53","doi-asserted-by":"publisher","first-page":"7857","DOI":"10.1074\/jbc.M112.423954","volume":"288","author":"BR Fluharty","year":"2013","unstructured":"Fluharty, B. R. et al. An N-terminal fragment of the prion protein binds to amyloid-beta oligomers and inhibits their neurotoxicity in vivo. J Biol Chem \n                           288, 7857\u20137866, doi:10.1074\/jbc.M112.423954 (2013).","journal-title":"J Biol Chem"},{"key":"10875_CR54","doi-asserted-by":"publisher","first-page":"655","DOI":"10.1111\/j.1462-5822.2007.01073.x","volume":"10","author":"E Marini","year":"2008","unstructured":"Marini, E. et al. HIV-1 matrix protein p17 binds to monocytes and selectively stimulates MCP-1 secretion: role of transcriptional factor AP-1. Cell Microbiol \n                           10, 655\u2013666, doi:10.1111\/j.1462-5822.2007.01073.x (2008).","journal-title":"Cell Microbiol"},{"key":"10875_CR55","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1046\/j.1365-2141.2003.04053.x","volume":"120","author":"M Vitale","year":"2003","unstructured":"Vitale, M. et al. HIV-1 matrix protein p17 enhances the proliferative activity of natural killer cells and increases their ability to secrete proinflammatory cytokines. Br J Haematol \n                           120, 337\u2013343 (2003).","journal-title":"Br J Haematol"},{"key":"10875_CR56","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1016\/j.smim.2014.04.005","volume":"26","author":"MA Ermolaeva","year":"2014","unstructured":"Ermolaeva, M. A. & Schumacher, B. Insights from the worm: the C. elegans model for innate immunity. Semin Immunol \n                           26, 303\u2013309, doi:10.1016\/j.smim.2014.04.005 (2014).","journal-title":"Semin Immunol"},{"key":"10875_CR57","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1189\/jlb.69.2.297","volume":"69","author":"TS Liang","year":"2001","unstructured":"Liang, T. S. et al. Cloning, mRNA distribution, and functional expression of an avian counterpart of the chemokine receptor\/HIV coreceptor CXCR4. J Leukoc Biol \n                           69, 297\u2013305 (2001).","journal-title":"J Leukoc Biol"},{"key":"10875_CR58","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1093\/gerona\/glv005","volume":"71","author":"Y Garcia-Mesa","year":"2016","unstructured":"Garcia-Mesa, Y. et al. Oxidative Stress Is a Central Target for Physical Exercise Neuroprotection Against Pathological Brain Aging. The journals of gerontology. Series A, Biological sciences and medical sciences \n                           71, 40\u201349, doi:10.1093\/gerona\/glv005 (2016).","journal-title":"The journals of gerontology. Series A, Biological sciences and medical sciences"},{"key":"10875_CR59","doi-asserted-by":"publisher","first-page":"961","DOI":"10.1111\/cns.12312","volume":"20","author":"S Revilla","year":"2014","unstructured":"Revilla, S. et al. Lenti-GDNF gene therapy protects against Alzheimer\u2019s disease-like neuropathology in 3xTg-AD mice and MC65 cells. CNS neuroscience & therapeutics \n                           20, 961\u2013972, doi:10.1111\/cns.12312 (2014).","journal-title":"CNS neuroscience & therapeutics"},{"key":"10875_CR60","doi-asserted-by":"publisher","first-page":"158","DOI":"10.1016\/j.mad.2005.09.016","volume":"127","author":"A Lanari","year":"2006","unstructured":"Lanari, A., Amenta, F., Silvestrelli, G., Tomassoni, D. & Parnetti, L. Neurotransmitter deficits in behavioural and psychological symptoms of Alzheimer\u2019s disease. Mechanisms of ageing and development \n                           127, 158\u2013165, doi:10.1016\/j.mad.2005.09.016 (2006).","journal-title":"Mechanisms of ageing and development"},{"key":"10875_CR61","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1016\/S0165-0173(01)00067-4","volume":"36","author":"R D\u2019Hooge","year":"2001","unstructured":"D\u2019Hooge, R. & De Deyn, P. P. Applications of the Morris water maze in the study of learning and memory. Brain research. Brain research reviews \n                           36, 60\u201390 (2001).","journal-title":"Brain research. Brain research reviews"},{"key":"10875_CR62","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1101\/lm.1650110","volume":"17","author":"NJ Broadbent","year":"2010","unstructured":"Broadbent, N. J., Gaskin, S., Squire, L. R. & Clark, R. E. Object recognition memory and the rodent hippocampus. Learn Mem \n                           17, 5\u201311, doi:10.1101\/lm.1650110 (2010).","journal-title":"Learn Mem"},{"key":"10875_CR63","doi-asserted-by":"publisher","unstructured":"Corpas, R. et al. SIRT1 Overexpression in Mouse Hippocampus Induces Cognitive Enhancement Through Proteostatic and Neurotrophic Mechanisms. Mol Neurobiol, doi:10.1007\/s12035-016-0087-9 (2016).","DOI":"10.1007\/s12035-016-0087-9"},{"key":"10875_CR64","doi-asserted-by":"publisher","first-page":"664","DOI":"10.18632\/aging.100906","volume":"8","author":"C Grinan-Ferre","year":"2016","unstructured":"Grinan-Ferre, C. et al. Epigenetic mechanisms underlying cognitive impairment and Alzheimer disease hallmarks in 5XFAD mice. Aging (Albany NY) \n                           8, 664\u2013684, doi:10.18632\/aging.100906 (2016).","journal-title":"Aging (Albany NY)"},{"key":"10875_CR65","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0001888","volume":"3","author":"A De Luigi","year":"2008","unstructured":"De Luigi, A. et al. The efficacy of tetracyclines in peripheral and intracerebral prion infection. PLoS One \n                           3, e1888, doi:10.1371\/journal.pone.0001888 (2008).","journal-title":"PLoS One"},{"key":"10875_CR66","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0052314","volume":"7","author":"L Diomede","year":"2012","unstructured":"Diomede, L. et al. C. elegans expressing human beta2-microglobulin: a novel model for studying the relationship between the molecular assembly and the toxic phenotype. PLoS One \n                           7, e52314, doi:10.1371\/journal.pone.0052314 (2012).","journal-title":"PLoS One"},{"key":"10875_CR67","doi-asserted-by":"publisher","first-page":"150","DOI":"10.1016\/S1474-4422(13)70307-7","volume":"13","author":"S Haik","year":"2014","unstructured":"Haik, S. et al. Doxycycline in Creutzfeldt-Jakob disease: a phase 2, randomised, double-blind, placebo-controlled trial. Lancet Neurol \n                           13, 150\u2013158, doi:10.1016\/S1474-4422(13)70307-7 (2014).","journal-title":"Lancet Neurol"},{"key":"10875_CR68","doi-asserted-by":"publisher","first-page":"334","DOI":"10.1002\/bip.20130","volume":"76","author":"S Fiorentini","year":"2004","unstructured":"Fiorentini, S. et al. Preclinical studies on immunogenicity of the HIV-1 p17-based synthetic peptide AT20-KLH. Biopolymers \n                           76, 334\u2013343, doi:10.1002\/bip.20130 (2004).","journal-title":"Biopolymers"},{"key":"10875_CR69","doi-asserted-by":"publisher","first-page":"4758","DOI":"10.1016\/j.vaccine.2008.06.082","volume":"26","author":"S Fiorentini","year":"2008","unstructured":"Fiorentini, S. et al. Synthetic peptide AT20 coupled to KLH elicits antibodies against a conserved conformational epitope from a major functional area of the HIV-1 matrix protein p17. Vaccine \n                           26, 4758\u20134765, doi:10.1016\/j.vaccine.2008.06.082 (2008).","journal-title":"Vaccine"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-10875-0","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-10875-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-10875-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,23]],"date-time":"2022-12-23T10:12:40Z","timestamp":1671790360000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-10875-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,9,4]]},"references-count":69,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2017,12]]}},"alternative-id":["10875"],"URL":"https:\/\/doi.org\/10.1038\/s41598-017-10875-0","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,9,4]]},"assertion":[{"value":"22 February 2017","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 August 2017","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 September 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":"10313"}}