{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T10:31:27Z","timestamp":1792405887729,"version":"4.4.0"},"reference-count":46,"publisher":"National Academy of Sciences","issue":"3","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2014,1,21]]},"abstract":"<jats:title>Significance<\/jats:title>\n                  <jats:p>\n                    Parkinsonism-dementia (PD) of Guam is a classical tauopathy in which abnormal hyperphosphorylation of tau leads to neurodegeneration and dementia. A key unresolved question is the mechanism of abnormal hyperphosphorylation of tau in this disease. This study reports the involvement of a signaling pathway in which the inhibition of protein phosphatase 2A (PP2A) through phosphorylation of its catalytic subunit PP2Ac at Tyr\n                    <jats:sup>307<\/jats:sup>\n                    induced by the activation of metabotropic glutamate receptor 5 (mGluR5) leads to hyperphosphorylation of tau. These findings suggest that the mGluR5\u2013PP2A axis has a central role in neurofibrillary degeneration in Guam PD and thus may be a therapeutic target for the treatment of this disease and related tauopathies.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1322614111","type":"journal-article","created":{"date-parts":[[2014,1,6]],"date-time":"2014-01-06T23:30:23Z","timestamp":1389051023000},"page":"1144-1149","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":88,"title":["Tau pathology involves protein phosphatase 2A in Parkinsonism-dementia of Guam"],"prefix":"10.1073","volume":"111","author":[{"given":"Mohammad","family":"Arif","sequence":"first","affiliation":[{"name":"Department of Neurochemistry, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY 10314;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Syed Faraz","family":"Kazim","sequence":"additional","affiliation":[{"name":"Department of Neurochemistry, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY 10314;"},{"name":"Neural and Behavioral Science Graduate Program, State University of New York Downstate Medical Center, Brooklyn, NY 11203; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inge","family":"Grundke-Iqbal","sequence":"additional","affiliation":[{"name":"Department of Neurochemistry, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY 10314;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralph M.","family":"Garruto","sequence":"additional","affiliation":[{"name":"Graduate Program in Biomedical Anthropology, Departments of Anthropology and Biological Sciences, Binghamton University, State University of New York, Binghamton, NY 13902"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khalid","family":"Iqbal","sequence":"additional","affiliation":[{"name":"Department of Neurochemistry, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY 10314;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2014,1,6]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.35.2.193"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.1962.04210030065009"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.neuro.24.1.1121"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-009-0486-3"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.2005.04391.x"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.1995.65020732.x"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.58.11.1871"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddl463"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0404.2008.01150.x"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.etap.2013.04.007"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.3603037"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2006.04.017"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1097\/WNR.0b013e32834fe6d6"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2006.10.002"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2009.04.002"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5351-09.2010"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-8741(02)00170-8"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2011.01.056"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)62486-8"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1093\/jnen\/63.4.287"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M112.446070"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1325671"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2008.05.013"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi00006a020"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(20)80536-5"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/kfp062"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)82288-8"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M411709200"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(87)90757-4"},{"key":"e_1_3_3_30_2","article-title":"Alzheimer disease and amyotrophic lateral sclerosis: An etiopathogenic connection","author":"Wang X","year":"2013","unstructured":"X Wang, et al., Alzheimer disease and amyotrophic lateral sclerosis: An etiopathogenic connection. Acta Neuropathol, in press. (2013).","journal-title":"Acta Neuropathol"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2235808100"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1212\/01.WNL.0000078320.18564.9F"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0075376"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0404926101"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.3109\/17482960903269062"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0404.2004.00320.x"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1582-4934.2008.00249.x"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.121119298"},{"key":"e_1_3_3_39_2","first-page":"S124","article-title":"Maximal inhibition of tau binding to microtubules requires the phosphorylation of tau at both Thr 231 and Ser 262","volume":"19","author":"Sengupta A","year":"1998","unstructured":"A Sengupta, et al., Maximal inhibition of tau binding to microtubules requires the phosphorylation of tau at both Thr 231 and Ser 262. Neurobiol Aging 19, S124\u2013S524 (1998).","journal-title":"Neurobiol Aging"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/0014-5793(96)00485-1"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.110957"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1007\/s004010100423"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0912793107"},{"key":"e_1_3_3_44_2","first-page":"177","article-title":"Sequential changes of tau-site-specific phosphorylation during development of paired helical filaments","volume":"7","author":"Kimura T","year":"1996","unstructured":"T Kimura, et al., Sequential changes of tau-site-specific phosphorylation during development of paired helical filaments. Dementia 7, 177\u2013181 (1996).","journal-title":"Dementia"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.21-20-07985.2001"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.1996.tb01611.x"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.1322614111","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,16]],"date-time":"2022-04-16T09:42:17Z","timestamp":1650102137000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.1322614111"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,1,6]]},"references-count":46,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2014,1,21]]}},"alternative-id":["10.1073\/pnas.1322614111"],"URL":"https:\/\/doi.org\/10.1073\/pnas.1322614111","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,1,6]]},"assertion":[{"value":"2014-01-06","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}