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As such, drugs promoting this pathway could be useful for prevention of the disease. Along this line, we searched through a number of substances and unexpectedly found that a group of high\u2010energy compounds (<jats:styled-content style=\"fixed-case\">HEC<\/jats:styled-content>s), namely <jats:styled-content style=\"fixed-case\">ATP<\/jats:styled-content>, phosphocreatine, and acetyl coenzyme A, potently increased <jats:styled-content style=\"fixed-case\">APP<\/jats:styled-content> \u03b1\u2010processing in cultured <jats:styled-content style=\"fixed-case\">SH<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">SY<\/jats:styled-content>5Y cells, whereas their cognate counterparts, i.e., <jats:styled-content style=\"fixed-case\">ADP<\/jats:styled-content>, creatine, or coenzyme A did not show the same effects. Other <jats:styled-content style=\"fixed-case\">HEC<\/jats:styled-content>s such as <jats:styled-content style=\"fixed-case\">GTP<\/jats:styled-content>,<jats:styled-content style=\"fixed-case\"> CTP<\/jats:styled-content>, phosphoenol pyruvate, and S\u2010adenosylmethionine also promoted <jats:styled-content style=\"fixed-case\">APP<\/jats:styled-content> \u03b1\u2010processing with varying potencies and the effects were abolished by energy inhibitors rotenone or NaN<jats:sub>3<\/jats:sub>. The overall efficacy of the <jats:styled-content style=\"fixed-case\">HEC<\/jats:styled-content>s in the process ranged from three\u2010 to four\u2010fold, which was significantly greater than that exhibited by other physiological stimulators such as glutamate and nicotine. This suggested that the <jats:styled-content style=\"fixed-case\">HEC<\/jats:styled-content>s were perhaps the most efficient physiological stimulators for <jats:styled-content style=\"fixed-case\">APP<\/jats:styled-content> \u03b1\u2010processing. Moreover, the <jats:styled-content style=\"fixed-case\">HEC<\/jats:styled-content>s largely offset the inefficient <jats:styled-content style=\"fixed-case\">APP<\/jats:styled-content> \u03b1\u2010processing in aged human fibroblasts or in cells impaired by rotenone or H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>. Most importantly, some <jats:styled-content style=\"fixed-case\">HEC<\/jats:styled-content>s markedly boosted the survival rate of <jats:styled-content style=\"fixed-case\">SH<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">SY<\/jats:styled-content>5Y cells in the death process induced by energy suppression or oxidative stress. These findings suggest a new, energy\u2010dependent regulatory mechanism for the putative \u03b1\u2010secretase and thus will help substantially in its identification. At the same time, the study raises the possibility that the <jats:styled-content style=\"fixed-case\">HEC<\/jats:styled-content>s may be useful to energize and strengthen the aging brain cells to slow down the progression of Alzheimer's disease.<\/jats:p>","DOI":"10.1111\/j.1471-4159.2012.07923.x","type":"journal-article","created":{"date-parts":[[2012,8,21]],"date-time":"2012-08-21T10:51:12Z","timestamp":1345546272000},"page":"525-531","source":"Crossref","is-referenced-by-count":12,"title":["High\u2010energy compounds promote physiological processing of Alzheimer's amyloid\u2010\u03b2 precursor protein and boost cell survival in culture"],"prefix":"10.1111","volume":"123","author":[{"given":"Darrell R.","family":"Sawmiller","sequence":"first","affiliation":[{"name":"Aging Research Laboratory Bay Pines VA Healthcare System Bay Pines Florida USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huey T.","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Aging Research Laboratory Bay Pines VA Healthcare System Bay Pines Florida USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Olga","family":"Markov","sequence":"additional","affiliation":[{"name":"Aging Research Laboratory Bay Pines VA Healthcare System Bay Pines Florida USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ming","family":"Chen","sequence":"additional","affiliation":[{"name":"Aging Research Laboratory Bay Pines VA Healthcare System Bay Pines Florida USA"},{"name":"Department of Molecular Pharmacology and Physiology University of South Florida, College of Medicine Tampa Florida USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2012,9,21]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2008.10.001"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12017-008-8053-y"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0005-2728(98)00114-5"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.2000.tb05576.x"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.3390\/ph2030287"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.87.15.6003"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M500219200"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.10389"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2202-11-144"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2004.02.052"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.490380111"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2008.09.001"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.2111583"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0403921101"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1385\/JMN:20:3:349"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10548-011-0170-5"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.18-20-08311.1998"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(17)36875-8"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2006.04368.x"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.2165\/11595870-000000000-00000"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2005.03493.x"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00702-004-0176-1"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.22.14015"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M505625200"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1124\/mol.52.3.430"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1037\/0735-7044.112.5.1199"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm0895-829"},{"key":"e_1_2_8_29_1","volume-title":"Biochemistry","author":"Lehninger A. 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