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The activity of protein phosphatase (PP)\u20102A is compromised in AD brain and is believed to be a cause of the abnormal hyperphosphorylation of tau and the consequent neurofibrillary degeneration. Here we show that memantine inhibits and reverses the PP\u20102A inhibition\u2010induced abnormal hyperphosphorylation and accumulation of tau in organotypic culture of rat hippocampal slices. Such restorative effects of memantine were not detected either with 5,7\u2010dichlorokynurenic acid or with <jats:sc>d<\/jats:sc>(\u2212)\u20102\u2010amino\u20105\u2010phosphopentanoic acid, NMDA receptor antagonists active at the glycine binding site and at the glutamate binding site, respectively. These findings show (1) that memantine inhibits and reverses the PP\u20102A inhibition\u2010induced abnormal hyperphosphorylation of tau\/neurofibrillary degeneration and (2) that this drug might be useful for the treatment of AD and related tauopathies.<\/jats:p>","DOI":"10.1016\/j.febslet.2004.04.047","type":"journal-article","created":{"date-parts":[[2004,5,11]],"date-time":"2004-05-11T10:36:08Z","timestamp":1084271768000},"page":"261-269","source":"Crossref","is-referenced-by-count":111,"title":["Memantine inhibits and reverses the Alzheimer type abnormal hyperphosphorylation of tau and associated neurodegeneration"],"prefix":"10.1002","volume":"566","author":[{"given":"Liang","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amitabha","family":"Sengupta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niloufar","family":"Haque","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inge","family":"Grundke-Iqbal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khalid","family":"Iqbal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2004,5,10]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/0022-510X(70)90063-8"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2990.1999.00182.x"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.83.13.4913"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(17)42989-9"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm0796-783"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.1.298"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.270.9.4854"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.275.8.5535"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(01)02127-5"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.1993.tb03603.x"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.1995.65020732.x"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.21-20-07985.2001"},{"key":"e_1_2_6_14_1","first-page":"14135","author":"Winblad B.","year":"1999","journal-title":"J. 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