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Cellular modulators of APP processing are well known from studies of genetic mutations (such as those found in APP and presenilins) or polymorphisms (such as the apolipoprotein\u2003E4 \u025b\u2010allele) that predisposes an individual to early or late\u2010onset Alzheimer's disease. In recent years, several classes of molecule with modulating functions in APP processing and A\u03b2 secretion have emerged. These include the neuronal Munc\u201018 interacting proteins (Mints)\/X11s, members of the reticulon family (RTN\u20103 and RTN\u20104\/Nogo\u2010B), the Nogo\u201066 receptor (NgR), the peptidyl\u2010prolyl isomerase Pin1 and the Rho family GTPases and their effectors. Mints and NgR bind to APP directly, while RTN3 and Nogo\u2010B interact with the \u03b2\u2010secretase BACE1. Phosphorylated APP is a Pin1 substrate, which binds to its phosphor\u2010Thr668\u2010Pro motif. These interactions by and large resulted in a reduction of A\u03b2 generation both <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic>. Inhibition of Rho and Rho\u2010kinase (ROCK) activity may underlie the ability of non\u2010steroidal anti\u2010inflammatory drugs and statins to reduce A\u03b2 production, a feat which could also be achieved by Rac1 inhibition. Detailed understanding of the underlying mechanisms of action of these novel modulators of APP processing, as well as insights into the molecular neurological basis of how A\u03b2 impairs leaning and memory, will open up multiple avenues for the therapeutic intervention of Alzheimer's disease.<\/jats:p>","DOI":"10.1111\/j.1471-4159.2006.04215.x","type":"journal-article","created":{"date-parts":[[2006,12,5]],"date-time":"2006-12-05T14:38:09Z","timestamp":1165329489000},"page":"314-323","source":"Crossref","is-referenced-by-count":45,"title":["Novel modulators of amyloid\u2010\u03b2 precursor protein processing"],"prefix":"10.1111","volume":"100","author":[{"given":"Bor Luen","family":"Tang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yih Cherng","family":"Liou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2006,10,2]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1020"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2005.08.130"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.10737"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M104059200"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M201308200"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddh077"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm1616"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.24.14761"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81736-5"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1058783"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M402248200"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M309561200"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2004.03.011"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1750-3639.2005.tb00101.x"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(03)00205-8"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)64113-2"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M507913200"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1042\/BST20051101"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb960"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200207113"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI18162"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1080\/10401230500296428"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M601849200"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2004.02743.x"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M211899200"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/s000180050299"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7600926"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.1999.0730985.x"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0705688"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1072994"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7600061"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M502861200"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1088"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M508460200"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M600728200"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.2174\/1389450033490902"},{"key":"e_1_2_10_38_1","doi-asserted-by":"crossref","first-page":"47\u2003863","DOI":"10.1074\/jbc.M104068200","article-title":"Angiotensin\u2010converting enzyme degrades Alzheimer amyloid \u03b2\u2010peptide (A\u03b2); retards A\u03b2 aggregation, deposition, fibril formation; and inhibits cytotoxicity","volume":"276","author":"Hu J.","year":"2001","journal-title":"J. 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