{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T21:37:29Z","timestamp":1790372249239,"version":"4.1.0"},"reference-count":62,"publisher":"Wiley","issue":"13","license":[{"start":{"date-parts":[[2006,11,1]],"date-time":"2006-11-01T00:00:00Z","timestamp":1162339200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2006,11]]},"abstract":"<jats:p>\n                    Many neurodegenerative diseases associated with functional\n                    <jats:italic>Tau<\/jats:italic>\n                    dysregulation, including Alzheimer's disease (AD) and other tauopathies, also show \u03b1\u2010synuclein (\u03b1\u2010\n                    <jats:italic>Syn<\/jats:italic>\n                    ) pathology, a protein associated with Parkinson's disease (PD) pathology. Here we show that treatment of primary mesencephalic neurons (48 h) or subchronic treatment of wild\u2010type (WT) mice with the Parkinsonism\u2010inducing neurotoxin MPP\n                    <jats:sup>+<\/jats:sup>\n                    \/MPTP, results in selective dose\u2010dependent hyperphosphorylation of\n                    <jats:italic>Tau<\/jats:italic>\n                    at Ser396\/404 (PHF\u20101\u2010reactive\n                    <jats:italic>Tau<\/jats:italic>\n                    , p\u2010\n                    <jats:italic>Tau<\/jats:italic>\n                    ), with no changes in pSer202 but with nonspecific increases in pSer262 levels. The presence of \u03b1\n                    <jats:italic>\u2010Syn<\/jats:italic>\n                    was absolutely mandatory to observe MPP\n                    <jats:sup>+<\/jats:sup>\n                    \/MPTP\u2010induced increases in p\u2010\n                    <jats:italic>Tau<\/jats:italic>\n                    levels, since no alterations in p\u2010\n                    <jats:italic>Tau<\/jats:italic>\n                    were seen in transfected cells not expressing \u03b1\n                    <jats:italic>\u2010Syn<\/jats:italic>\n                    or in \u03b1\n                    <jats:italic>\u2010Syn<\/jats:italic>\n                    \u2010\n                    <jats:italic>\/<\/jats:italic>\n                    \u2010 mice. MPP\n                    <jats:sup>+<\/jats:sup>\n                    \/MPTP also induced a significant accumulation of \u03b1\n                    <jats:italic>\u2010Syn<\/jats:italic>\n                    in both mesencephalic neurons and in WT mice striatum. MPTP\/MPP\n                    <jats:sup>+<\/jats:sup>\n                    lead to differential alterations in p\u2010\n                    <jats:italic>Tau<\/jats:italic>\n                    and \u03b1\n                    <jats:italic>\u2010Syn<\/jats:italic>\n                    levels in a cytoskeleton\u2010bound,\n                    <jats:italic>vs<\/jats:italic>\n                    . a soluble, cytoskeleton\u2010free fraction, inducing their coimmunoprecipitation in the cytoskeleton\u2010free fraction and neuronal soma. Subchronic MPTP exposure increased sarkosyl\u2010insoluble p\u2010\n                    <jats:italic>Tau<\/jats:italic>\n                    in striatum of WT but not \u03b1\n                    <jats:italic>\u2010Syn<\/jats:italic>\n                    \u2010\n                    <jats:italic>\/<\/jats:italic>\n                    \u2010 mice. These studies describe a novel mechanism for MPTP neurotoxicity, namely a MPTP\u2010inducible, strictly \u03b1\n                    <jats:italic>\u2010Syn<\/jats:italic>\n                    \u2010dependent, increased formation of PHF\u20101\u2010reactive\n                    <jats:italic>Tau<\/jats:italic>\n                    , suggesting convergent overlapping pathways in the genesis of clinically divergent diseases such as AD and PD. \u2014Duka, T., Rusnak, M., Drolet, R. E., Duka, V., Wersinger, C., Goudreau, J. L., Sidhu, A. Alpha\u2010synuclein induces hyperphosphorylation of Tau in the MPTP model of Parkinsonism.\n                    <jats:italic>FASEB J.<\/jats:italic>\n                    20, 2302\u20132312 (2006)\n                  <\/jats:p>","DOI":"10.1096\/fj.06-6092com","type":"journal-article","created":{"date-parts":[[2006,10,31]],"date-time":"2006-10-31T16:51:21Z","timestamp":1162313481000},"page":"2302-2312","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":99,"title":["Alpha\u2010Synuclein induces hyperphosphorylation of Tau in the MPTP model of Parkinsonism"],"prefix":"10.1096","volume":"20","author":[{"given":"Tetyana","family":"Duka","sequence":"first","affiliation":[{"name":"Department of Biochemistry Molecular and Cellular Biology Georgetown University Washington, DC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milan","family":"Rusnak","sequence":"additional","affiliation":[{"name":"Department of Biochemistry Molecular and Cellular Biology Georgetown University Washington, DC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert E.","family":"Drolet","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology Michigan State University East Lansing Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valeriy","family":"Duka","sequence":"additional","affiliation":[{"name":"Department of Biochemistry Molecular and Cellular Biology Georgetown University Washington, DC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christophe","family":"Wersinger","sequence":"additional","affiliation":[{"name":"Department of Biochemistry Molecular and Cellular Biology Georgetown University Washington, DC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John L.","family":"Goudreau","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology Michigan State University East Lansing Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anita","family":"Sidhu","sequence":"additional","affiliation":[{"name":"Department of Biochemistry Molecular and Cellular Biology Georgetown University Washington, DC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2006,11]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1080\/07853890510007269"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0298-106"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2005.10.019"},{"key":"e_1_2_6_5_1","doi-asserted-by":"crossref","DOI":"10.1126\/science.1090278","article-title":"alpha\u2010Synuclein locus triplication causes Parkinson's disease","author":"Singleton A.B.","year":"2003","journal-title":"Science"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(04)17103-1"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-4547(19991001)58:1<120::AID-JNR12>3.0.CO;2-E"},{"key":"e_1_2_6_8_1","doi-asserted-by":"crossref","first-page":"932","DOI":"10.1038\/nrn983","article-title":"Pathogenesis of Parkinson's disease: dopamine, vesicles and alpha\u2010synuclein","volume":"12","author":"Lotharius J.","year":"2002","journal-title":"Nat. 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