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The fact that hyperphosphorylation of tau in NFTs are also found in the patients with Niemann\u2013Pick disease, type C (NPC), which is a cholesterol storage disease associated with defective intracellular trafficking of exogenous cholesterol, implies that perturbation of cholesterol metabolism may be involved in tau phosphorylation and neurodegeneration. Here, we report that cholesterol deficiency induced by inhibition of cholesterol biosynthesis in cultured neurons results in hyperphosphorylation of tau, accompanied by axonal degeneration associated with microtubule depolymerization. These changes were prevented by concurrent treatment with \u03b2\u2010migrating very low\u2010density lipoprotein (\u03b2\u2010VLDL) or cholesterol. We propose that intracellular cholesterol plays an essential role in the modulation of tau phosphorylation and the maintenance of microtubule stability.<\/jats:p>","DOI":"10.1046\/j.1471-4159.2001.00063.x","type":"journal-article","created":{"date-parts":[[2003,3,12]],"date-time":"2003-03-12T06:50:39Z","timestamp":1047451839000},"page":"391-400","source":"Crossref","is-referenced-by-count":107,"title":["Cholesterol\u2010dependent modulation of tau phosphorylation in cultured neurons"],"prefix":"10.1111","volume":"76","author":[{"given":"Qi\u2010Wen","family":"Fan","sequence":"first","affiliation":[]},{"given":"Wei","family":"Yu","sequence":"additional","affiliation":[]},{"given":"Takao","family":"Senda","sequence":"additional","affiliation":[]},{"given":"Katsuhiko","family":"Yanagisawa","sequence":"additional","affiliation":[]},{"given":"Makoto","family":"Michikawa","sequence":"additional","affiliation":[]}],"member":"311","published-online":{"date-parts":[[2008,8,15]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.12.5562"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm0796-783"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s004010050368"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(93)90279-Z"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj3230577"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.76.1.514"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(93)90057-X"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.277.5323.228"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.275.6.4013"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)82288-8"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.08-04-01454.1988"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.3.10.1141"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0968-0004(98)01245-6"},{"key":"e_1_2_7_15_1","volume-title":"Guidebook to the Cytoskeletal and Motor Proteins and to the Extracellular Matrix and Adhesion Proteins","author":"Friedhoff P.","year":"1998"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/0166-2236(93)90078-Z"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/0166-2236(91)90105-4"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(92)90117-V"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj3010871"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.1995.65062804.x"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.1995.65020732.x"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.275.8.5535"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)48531-6"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(17)38495-8"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.83.13.4913"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.142.1.167"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/369488a0"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M001793200"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/0955-0674(94)90119-8"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.19-17-07486.1999"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(88)90129-8"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1899488"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.277.5323.232"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.34.21901"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(17)42989-9"},{"key":"e_1_2_7_36_1","doi-asserted-by":"crossref","first-page":"1639","DOI":"10.1016\/S0022-2275(20)37182-0","article-title":"Inhibition of cholesterol biosynthesis by squalene epoxidase inhibitor avoids apoptotic cell death in L6 myoblasts","volume":"38","author":"Matzuno S.","year":"1997","journal-title":"J. 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