{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T00:32:59Z","timestamp":1791419579188,"version":"4.3.3"},"reference-count":52,"publisher":"Elsevier BV","issue":"16","license":[{"start":{"date-parts":[[2013,4,1]],"date-time":"2013-04-01T00:00:00Z","timestamp":1364774400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2020,9,18]],"date-time":"2020-09-18T00:00:00Z","timestamp":1600387200000},"content-version":"vor","delay-in-days":2727,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Biological Chemistry"],"published-print":{"date-parts":[[2013,4]]},"DOI":"10.1074\/jbc.m112.436006","type":"journal-article","created":{"date-parts":[[2013,2,27]],"date-time":"2013-02-27T02:27:03Z","timestamp":1361932023000},"page":"11024-11037","source":"Crossref","is-referenced-by-count":140,"title":["Aminothienopyridazines and Methylene Blue Affect Tau Fibrillization via Cysteine Oxidation"],"prefix":"10.1016","volume":"288","author":[{"given":"Alex","family":"Crowe","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J.","family":"James","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Virginia M.-Y.","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"III","given":"Amos B.","family":"Smith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John Q.","family":"Trojanowski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlo","family":"Ballatore","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kurt R.","family":"Brunden","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1074\/jbc.M112.436006_bib1","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1038\/197192b0","article-title":"Paired helical filaments in electron microscopy of Alzheimers disease","volume":"197","author":"Kidd","year":"1963","journal-title":"Nature"},{"key":"10.1074\/jbc.M112.436006_bib2","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1126\/science.1899488","article-title":"A68, a major subunit of paired helical filaments and derivatized forms of normal Tau","volume":"251","author":"Lee","year":"1991","journal-title":"Science"},{"key":"10.1074\/jbc.M112.436006_bib3","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","year":"2007","journal-title":"Nat. Rev. Neurosci."},{"key":"10.1074\/jbc.M112.436006_bib4","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1146\/annurev.neuro.24.1.1121","article-title":"Neurodegenerative tauopathies","volume":"24","author":"Lee","year":"2001","journal-title":"Annu. Rev. Neurosci."},{"key":"10.1074\/jbc.M112.436006_bib5","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1038\/31508","article-title":"Association of missense and 5\u2032-splice-site mutations in Tau with the inherited dementia FTDP-17","volume":"393","author":"Hutton","year":"1998","journal-title":"Nature"},{"key":"10.1074\/jbc.M112.436006_bib6","doi-asserted-by":"crossref","first-page":"1914","DOI":"10.1126\/science.282.5395.1914","article-title":"Mutation-specific functional impairments in distinct Tau isoforms of hereditary FTDP-17","volume":"282","author":"Hong","year":"1998","journal-title":"Science"},{"key":"10.1074\/jbc.M112.436006_bib7","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1016\/0022-2836(77)90214-5","article-title":"Physical and chemical properties of purified Tau factor and role of Tau in microtubule assembly","volume":"116","author":"Cleveland","year":"1977","journal-title":"J. Mol. Biol."},{"key":"10.1074\/jbc.M112.436006_bib8","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/0022-2836(77)90213-3","article-title":"Purification of tau, a microtubule-associated protein that induces assembly of microtubules from purified tubulin","volume":"116","author":"Cleveland","year":"1977","journal-title":"J. Mol. Biol."},{"key":"10.1074\/jbc.M112.436006_bib9","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1016\/0022-510X(82)90155-1","article-title":"Plaques, tangles, and dementia. A quantitative study","volume":"56","author":"Wilcock","year":"1982","journal-title":"J. Neurol. Sci."},{"key":"10.1074\/jbc.M112.436006_bib10","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1212\/WNL.42.3.631","article-title":"Neurofibrillary tangles but not senile plaques parallel duration and severity of Alzheimers disease","volume":"42","author":"Arriagada","year":"1992","journal-title":"Neurology"},{"key":"10.1074\/jbc.M112.436006_bib11","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1007\/BF00308809","article-title":"Neuropathological staging of Alzheimer-related changes","volume":"82","author":"Braak","year":"1991","journal-title":"Acta Neuropathol."},{"key":"10.1074\/jbc.M112.436006_bib12","doi-asserted-by":"crossref","first-page":"393","DOI":"10.3233\/JAD-2008-14406","article-title":"Evidence that non-fibrillar Tau causes pathology linked to neurodegeneration and behavioral impairments","volume":"14","author":"Brunden","year":"2008","journal-title":"J. Alzheimers Dis."},{"key":"10.1074\/jbc.M112.436006_bib13","doi-asserted-by":"crossref","first-page":"S87","DOI":"10.1016\/0197-4580(94)90179-1","article-title":"Microtubule stabilizing drugs for the treatment of Alzheimers disease","volume":"15","author":"Lee","year":"1994","journal-title":"Neurobiol. Aging"},{"key":"10.1074\/jbc.M112.436006_bib14","doi-asserted-by":"crossref","first-page":"2922","DOI":"10.1016\/j.febslet.2006.02.067","article-title":"Tau phosphorylation and aggregation in Alzheimer's disease pathology","volume":"580","author":"Avila","year":"2006","journal-title":"FEBS Lett."},{"key":"10.1074\/jbc.M112.436006_bib15","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1016\/j.expneurol.2009.08.031","article-title":"Tau-directed drug discovery for Alzheimer's disease and related tauopathies. A focus on Tau assembly inhibitors","volume":"223","author":"Brunden","year":"2010","journal-title":"Exp. Neurol."},{"key":"10.1074\/jbc.M112.436006_bib16","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1038\/nrd2959","article-title":"Advances in tau-focused drug discovery for Alzheimer's disease and related tauopathies","volume":"8","author":"Brunden","year":"2009","journal-title":"Nat. Rev. Drug Discov."},{"key":"10.1074\/jbc.M112.436006_bib17","doi-asserted-by":"crossref","first-page":"10278","DOI":"10.1073\/pnas.0401911101","article-title":"Template-assisted filament growth by parallel stacking of Tau","volume":"101","author":"Margittai","year":"2004","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"10.1074\/jbc.M112.436006_bib18","doi-asserted-by":"crossref","first-page":"13806","DOI":"10.1074\/jbc.M800247200","article-title":"Nucleation-dependent Tau filament formation. The importance of dimerization and an estimation of elementary rate constants","volume":"283","author":"Congdon","year":"2008","journal-title":"J. Biol. Chem."},{"key":"10.1074\/jbc.M112.436006_bib19","doi-asserted-by":"crossref","first-page":"25644","DOI":"10.1074\/jbc.M301663200","article-title":"Anionic micelles and vesicles induce Tau fibrillization in vitro","volume":"278","author":"Chirita","year":"2003","journal-title":"J. Biol. Chem."},{"key":"10.1074\/jbc.M112.436006_bib20","first-page":"2181","article-title":"Free fatty acids stimulate the polymerization of Tau and amyloid beta peptides. In vitro evidence for a common effector of pathogenesis in Alzheimer's disease","volume":"150","author":"Wilson","year":"1997","journal-title":"Am. J. Pathol."},{"key":"10.1074\/jbc.M112.436006_bib21","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1038\/383550a0","article-title":"Assembly of microtubule-associated protein Tau into Alzheimer-like filaments induced by sulphated glycosaminoglycans","volume":"383","author":"Goedert","year":"1996","journal-title":"Nature"},{"key":"10.1074\/jbc.M112.436006_bib22","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1083\/jcb.118.3.573","article-title":"Alzheimer-like paired helical filaments and antiparallel dimers formed from microtubule-associated protein Tau in vitro","volume":"118","author":"Wille","year":"1992","journal-title":"J. Cell Biol."},{"key":"10.1074\/jbc.M112.436006_bib23","doi-asserted-by":"crossref","first-page":"317","DOI":"10.2174\/156802611794072605","article-title":"Modulation of protein-protein interactions as a therpeutic strategy for the treatment of neurodegenerative tauopathies","volume":"11","author":"Ballatore","year":"2011","journal-title":"Curr. Top. Med. Chem."},{"key":"10.1074\/jbc.M112.436006_bib24","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1016\/j.neuropharm.2010.01.016","article-title":"Tau protein and Tau aggregation inhibitors","volume":"59","author":"Bulic","year":"2010","journal-title":"Neuropharmacology"},{"key":"10.1074\/jbc.M112.436006_bib25","doi-asserted-by":"crossref","first-page":"T775","DOI":"10.1016\/j.jalz.2008.05.2417","article-title":"Tau aggregation inhibitor (TAI) therapy with rember arrests the trajectory of rCBF decline in brain regions affected by Tau pathology in mild to moderate Alzheimer's disease","volume":"4","author":"Staff","year":"2008","journal-title":"Alzheimer Dement."},{"key":"10.1074\/jbc.M112.436006_bib26","doi-asserted-by":"crossref","first-page":"7732","DOI":"10.1021\/bi9006435","article-title":"The identification of aminothienopyridazine inhibitors of Tau assembly by quantitative high-throughput screening","volume":"48","author":"Crowe","year":"2009","journal-title":"Biochemistry"},{"key":"10.1074\/jbc.M112.436006_bib27","doi-asserted-by":"crossref","first-page":"4451","DOI":"10.1016\/j.bmc.2012.05.027","article-title":"Aminothienopyridazine inhibitors of Tau aggregation. Evaluation of structure-activity relationship leads to selection of candidates with desirable in vivo properties","volume":"20","author":"Ballatore","year":"2012","journal-title":"Bioorg. Med. Chem."},{"key":"10.1074\/jbc.M112.436006_bib28","doi-asserted-by":"crossref","first-page":"3739","DOI":"10.1021\/jm100138f","article-title":"Discovery of brain-penetrant, orally bioavailable aminothienopyridazine inhibitors of Tau aggregation","volume":"53","author":"Ballatore","year":"2010","journal-title":"J. Med. Chem."},{"key":"10.1074\/jbc.M112.436006_bib29","doi-asserted-by":"crossref","first-page":"1339","DOI":"10.1111\/j.1471-4159.2009.06224.x","article-title":"Inhibition of Tau fibrillization by oleocanthal via reaction with the amino groups of Tau","volume":"110","author":"Li","year":"2009","journal-title":"J Neurochem."},{"key":"10.1074\/jbc.M112.436006_bib30","doi-asserted-by":"crossref","first-page":"14885","DOI":"10.1021\/bi026469j","article-title":"Toward a unified scheme for the aggregation of Tau into Alzheimer paired helical filaments","volume":"41","author":"Barghorn","year":"2002","journal-title":"Biochemistry"},{"key":"10.1074\/jbc.M112.436006_bib31","doi-asserted-by":"crossref","first-page":"11714","DOI":"10.1021\/bi000850r","article-title":"Structure, microtubule interactions, and paired helical filament aggregation by Tau mutants of frontotemporal dementias","volume":"39","author":"Barghorn","year":"2000","journal-title":"Biochemistry"},{"key":"10.1074\/jbc.M112.436006_bib32","doi-asserted-by":"crossref","first-page":"6657","DOI":"10.1021\/ja00017a044","article-title":"Disulfide bond formation in peptides by dimethyl sulfoxide. Scope and applications","volume":"113","author":"Tam","year":"1991","journal-title":"J. Am. Chem. Soc."},{"key":"10.1074\/jbc.M112.436006_bib33","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.bbrc.2007.03.056","article-title":"High throughput screening for small molecule inhibitors of heparin-induced Tau fibril formation","volume":"358","author":"Crowe","year":"2007","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"10.1074\/jbc.M112.436006_bib34","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1177\/108705719900400206","article-title":"A simple statistical parameter for use in evaluation and validation of high throughput screening assays","volume":"4","author":"Zhang","year":"1999","journal-title":"J. Biomol. Screen."},{"key":"10.1074\/jbc.M112.436006_bib35","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/0003-2697(82)90113-0","article-title":"Electrophoresis buffers for polyacrylamide gels at various pH","volume":"126","author":"McLellan","year":"1982","journal-title":"Anal. Biochem."},{"key":"10.1074\/jbc.M112.436006_bib36","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1016\/0003-2697(87)90064-9","article-title":"Fluorescent labeling of cysteinyl residues to facilitate electrophoretic isolation of proteins suitable for amino-terminal sequence analysis","volume":"160","author":"Gorman","year":"1987","journal-title":"Anal. Biochem."},{"key":"10.1074\/jbc.M112.436006_bib37","doi-asserted-by":"crossref","first-page":"9591","DOI":"10.1074\/jbc.M111.336107","article-title":"Using intramolecular disulfide bonds in Tau protein to deduce structural features of aggregation-resistant conformations","volume":"287","author":"Walker","year":"2012","journal-title":"J. Biol. Chem."},{"key":"10.1074\/jbc.M112.436006_bib38","doi-asserted-by":"crossref","first-page":"8463","DOI":"10.1073\/pnas.92.18.8463","article-title":"Oxidation of cysteine 322 in the repeat domain of microtubule-associated protein Tau controls the in vitro assembly of paired helical filaments","volume":"92","author":"Schweers","year":"1995","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"10.1074\/jbc.M112.436006_bib39","doi-asserted-by":"crossref","first-page":"1001","DOI":"10.1042\/bj3151001","article-title":"pH dependence of the dithiol-oxidizing activity of DsbA (a periplasmic protein thiol:disulphide oxidoreductase) and protein disulphide-isomerase. Studies with a novel simple peptide substrate","volume":"315","author":"Ruddock","year":"1996","journal-title":"Biochem. J."},{"key":"10.1074\/jbc.M112.436006_bib40","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1089\/adt.2009.0247","article-title":"Profiling the NIH small molecule repository for compounds that generate H2O2 by redox cycling in reducing environments","volume":"8","author":"Soares","year":"2010","journal-title":"Assay Drug Dev. Technol."},{"key":"10.1074\/jbc.M112.436006_bib41","doi-asserted-by":"crossref","first-page":"7614","DOI":"10.1074\/jbc.M408714200","article-title":"Inhibition of heparin-induced Tau filament formation by phenothiazines, polyphenols, and porphyrins","volume":"280","author":"Taniguchi","year":"2005","journal-title":"J. Biol. Chem."},{"key":"10.1074\/jbc.M112.436006_bib42","doi-asserted-by":"crossref","first-page":"3539","DOI":"10.1021\/jm900116d","article-title":"Structure-activity relationship of cyanine Tau aggregation inhibitors","volume":"52","author":"Chang","year":"2009","journal-title":"J. Med. Chem."},{"key":"10.1074\/jbc.M112.436006_bib43","doi-asserted-by":"crossref","first-page":"11213","DOI":"10.1073\/pnas.93.20.11213","article-title":"Selective inhibition of Alzheimer disease-like Tau aggregation by phenothiazines","volume":"93","author":"Wischik","year":"1996","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"10.1074\/jbc.M112.436006_bib44","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1002\/med.20177","article-title":"Cellular and molecular actions of methylene blue in the nervous system","volume":"31","author":"Oz","year":"2011","journal-title":"Med. Res. Rev."},{"key":"10.1074\/jbc.M112.436006_bib45","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1179\/joc.2002.14.5.431","article-title":"Methylene Blue. A therapeutic dye for all seasons?","volume":"14","author":"Wainwright","year":"2002","journal-title":"J. Chemother."},{"key":"10.1074\/jbc.M112.436006_bib46","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1016\/j.semcdb.2012.03.017","article-title":"Glutathione synthesis and its role in redox signaling","volume":"23","author":"Zhang","year":"2012","journal-title":"Semin. Cell Dev. Biol."},{"key":"10.1074\/jbc.M112.436006_bib47","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1006\/abbi.2002.2757","article-title":"Expression, preparation, and high-throughput screening of caspase-8. Discovery of redox-based and steroid diacid inhibition","volume":"399","author":"Smith","year":"2002","journal-title":"Arch. Biochem. Biophys."},{"key":"10.1074\/jbc.M112.436006_bib48","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1111\/j.1440-1789.2006.00666.x","article-title":"Biochemistry and molecular biology of tauopathies","volume":"26","author":"Hasegawa","year":"2006","journal-title":"Neuropathology"},{"key":"10.1074\/jbc.M112.436006_bib49","doi-asserted-by":"crossref","first-page":"2325","DOI":"10.1016\/j.neurobiolaging.2010.12.012","article-title":"\u201cLest we forget you \u201cmethylene blue. \u201d","volume":"32","author":"Schirmer","year":"2011","journal-title":"Neurobiol. Aging"},{"key":"10.1074\/jbc.M112.436006_bib50","doi-asserted-by":"crossref","first-page":"12079","DOI":"10.1523\/JNEUROSCI.3345-09.2009","article-title":"Chemical manipulation of Hsp70 ATPase activity regulates Tau stability","volume":"29","author":"Jinwal","year":"2009","journal-title":"J. Neurosci."},{"key":"10.1074\/jbc.M112.436006_bib51","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1186\/1750-1326-5-45","article-title":"Phenothiazine-mediated rescue of cognition in Tau transgenic mice requires neuroprotection and reduced soluble Tau burden","volume":"5","author":"O'Leary","year":"2010","journal-title":"Mol. Neurodegener."},{"key":"10.1074\/jbc.M112.436006_bib52","doi-asserted-by":"crossref","first-page":"609","DOI":"10.4161\/auto.19048","article-title":"Methylthioninium chloride (methylene blue) induces autophagy and attenuates tauopathy in vitroin vivo","volume":"8","author":"Congdon","year":"2012","journal-title":"Autophagy"}],"container-title":["Journal of Biological Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0021925820671836?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0021925820671836?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1074\/jbc.M112.436006","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,1,5]],"date-time":"2022-01-05T10:19:15Z","timestamp":1641377955000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0021925820671836"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,4]]},"references-count":52,"journal-issue":{"issue":"16","published-print":{"date-parts":[[2013,4]]}},"alternative-id":["S0021925820671836"],"URL":"https:\/\/doi.org\/10.1074\/jbc.m112.436006","relation":{},"ISSN":["0021-9258"],"issn-type":[{"value":"0021-9258","type":"print"}],"subject":[],"published":{"date-parts":[[2013,4]]}}}