{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T04:46:01Z","timestamp":1782881161050,"version":"3.54.5"},"reference-count":36,"publisher":"FapUNIFESP (SciELO)","issue":"10","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arq. Neuro-Psiquiatr."],"abstract":"<jats:p>ABSTRACT Protein misfolding diseases are usually associated with deposits of single \u201ckey\u201d proteins that somehow drive the pathology; \u03b2-amyloid and hyperphosphorylated tau accumulate in Alzheimer's disease, \u03b1-synuclein in Parkinson's disease, or abnormal prion protein (PrPTSE) in transmissible spongiform encephalopathies (TSEs or prion diseases). However, in some diseases more than two proteins accumulate in the same brain. These diseases might be considered \u201ccomplex\u201d proteinopathies. We have studied models of TSEs (to explore deposits of PrPTSE and of \u201csecondary proteins\u201d) infecting different strains and doses of TSE agent, factors that control incubation period, duration of illness and histopathology. Model TSEs allowed us to investigate whether different features of histopathology are independent of PrPTSE or appear as a secondary result of PrPTSE. Better understanding the complex proteinopathies may help to explain the wide spectrum of degenerative diseases and why some overlap clinically and histopathologically. These studies might also improve diagnosis and eventually even suggest new treatments for human neurodegenerative diseases.<\/jats:p>","DOI":"10.1590\/0004-282x20180111","type":"journal-article","created":{"date-parts":[[2018,11,22]],"date-time":"2018-11-22T11:43:32Z","timestamp":1542887012000},"page":"705-712","source":"Crossref","is-referenced-by-count":4,"title":["Complex proteinopathies and neurodegeneration: insights from the study of transmissible spongiform encephalopathies"],"prefix":"10.1590","volume":"76","author":[{"given":"Pedro","family":"Piccardo","sequence":"first","affiliation":[{"name":"U.S. Food and Drug Administration, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David M.","family":"Asher","sequence":"additional","affiliation":[{"name":"U.S. Food and Drug Administration, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"530","published-online":{"date-parts":[[2018,10]]},"reference":[{"issue":"9","key":"ref1","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1038\/nrn2194","article-title":"Tau-mediated neurodegeneration in Alzheimer's disease and related disorders","volume":"8","author":"Ballatore C","year":"2007","journal-title":"Nat Rev Neurosci"},{"issue":"49","key":"ref2","doi-asserted-by":"crossref","first-page":"1448","DOI":"10.1021\/bi901855z","article-title":"Inverse correlation of thermal lability and conversion efficiency for five prion protein polymorphic variants","author":"Kirby L","year":"2010","journal-title":"Biochem"},{"issue":"4542","key":"ref3","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1126\/science.6801762","article-title":"Novel proteinaceous infectious particles cause scrapie","volume":"216","author":"Prusiner SB","year":"1982","journal-title":"Science"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1007\/978-1-4614-3704-8_27","article-title":"Characterization of oligomerization-aggregation products of neurodegenerative target proteins by ion mobility mass spectrometry","volume":"896","author":"Vlad C","year":"2012","journal-title":"Methods Mol Biol"},{"issue":"82","key":"ref5","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1016\/bs.apha.2017.09.007","article-title":"Synaptotoxic signaling by amyloid beta oligomers in Alzheimer's disease through prion protein and mGluR5","volume":"82","author":"Brody AH","year":"2018","journal-title":"Adv Pharmacol"},{"issue":"9","key":"ref6","doi-asserted-by":"crossref","first-page":"1227","DOI":"10.1038\/nn.3178","article-title":"Alzheimer amyloid-\u03b2 oligomer bound to postsynaptic prion protein activates Fyn to impair neurons","volume":"15","author":"Um JW","year":"2012","journal-title":"Nat Neurosci"},{"issue":"5619","key":"ref7","doi-asserted-by":"crossref","first-page":"636","DOI":"10.1126\/science.1082324","article-title":"Initiation and synergistic fibrillization of tau and alpha-synuclein","volume":"300","author":"Giasson BI","year":"2003","journal-title":"Science"},{"issue":"42","key":"ref8","doi-asserted-by":"crossref","first-page":"35222","DOI":"10.1074\/jbc.M112.348300","article-title":"Hyperphosphorylation of Tau induced by naturally secreted amyloid-\u03b2 at nanomolar concentrations is modulated by insulin-dependent Akt-GSK3\u03b2 signaling pathway","volume":"287","author":"Tokutake T","year":"2012","journal-title":"J Biol Chem"},{"issue":"4","key":"ref9","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1007\/s00401-015-1525-x","article-title":"Heterotypic seeding of Tau fibrillization by pre-aggregated Abeta provides potent seeds for prion-like seeding and propagation of Tau-pathology in vivo","volume":"131","author":"Vasconcelos B","year":"2016","journal-title":"Acta Neuropathol"},{"issue":"4","key":"ref10","doi-asserted-by":"crossref","first-page":"300","DOI":"10.2174\/1389202918666171005100549","article-title":"Decoding common features of neurodegenerative disorders: from differentially expressed genes to pathways","volume":"19","author":"Habib R","year":"2018","journal-title":"Curr Genomics"},{"issue":"Pt 8","key":"ref11","doi-asserted-by":"crossref","first-page":"2510","DOI":"10.1093\/brain\/awt171","article-title":"Dissecting phenotypic traits linked to human resilience to Alzheimer's pathology","volume":"136","author":"Perez-Nievas BG","year":"2013","journal-title":"Brain"},{"issue":"1","key":"ref12","doi-asserted-by":"crossref","DOI":"10.3390\/ijms17010082","article-title":"(Review). 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