{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T23:38:42Z","timestamp":1791329922628,"version":"4.3.1"},"reference-count":74,"publisher":"American Chemical Society (ACS)","issue":"12","license":[{"start":{"date-parts":[[2015,3,12]],"date-time":"2015-03-12T00:00:00Z","timestamp":1426118400000},"content-version":"vor","delay-in-days":365,"URL":"https:\/\/pubs.acs.org\/page\/policy\/authorchoice_termsofuse.html"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2014,4,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\u03b3-Secretase catalyzes the final cleavage of the amyloid precursor protein (APP), resulting in the production of amyloid-\u03b2 (A\u03b2) peptides with different carboxyl termini. Presenilin (PSEN) and amyloid precursor protein (APP) mutations linked to early onset familial Alzheimer\u2019s disease modify the profile of A\u03b2 isoforms generated, by altering both the initial \u03b3-secretase cleavage site and subsequent processivity in a manner that leads to increased levels of the more amyloidogenic A\u03b242 and in some circumstances A\u03b243. Compounds termed \u03b3-secretase modulators (GSMs) and inverse GSMs (iGSMs) can decrease and increase levels of A\u03b242, respectively. As GSMs lower the level of production of pathogenic forms of long A\u03b2 isoforms, they are of great interest as potential Alzheimer\u2019s disease therapeutics. The factors that regulate GSM modulation are not fully understood; however, there is a growing body of evidence that supports the hypothesis that GSM activity is influenced by the amino acid sequence of the \u03b3-secretase substrate. We have evaluated whether mutations near the luminal border of the transmembrane domain (TMD) of APP alter the ability of both acidic, nonsteroidal anti-inflammatory drug-derived carboxylate and nonacidic, phenylimidazole-derived classes of GSMs and iGSMs to modulate \u03b3-secretase cleavage. Our data show that point mutations can dramatically reduce the sensitivity to modulation of cleavage by GSMs but have weaker effects on iGSM activity. These studies support the concept that the effect of GSMs may be substrate selective; for APP, it is dependent on the amino acid sequence of the substrate near the junction of the extracellular domain and luminal segment of the TMD.<\/jats:p>","DOI":"10.1021\/bi401521t","type":"journal-article","created":{"date-parts":[[2014,3,12]],"date-time":"2014-03-12T15:41:20Z","timestamp":1394638880000},"page":"1947-1957","source":"Crossref","is-referenced-by-count":22,"title":["Complex Relationships between Substrate Sequence and Sensitivity to Alterations in \u03b3-Secretase Processivity Induced by \u03b3-Secretase Modulators"],"prefix":"10.1021","volume":"53","author":[{"given":"Joo In","family":"Jung","sequence":"first","affiliation":[{"name":"University of Florida , , , , , , , ,","place":["Gainesville, Florida, United States, 32603"]},{"name":"University of Florida , , , , , , , ,","place":["Gainesville, Florida, United States, 32603"]},{"name":"University of Florida , , , , , , , ,","place":["Gainesville, Florida, United States, 32603"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Ran","sequence":"additional","affiliation":[{"name":"University of Florida , , , , , , , ,","place":["Gainesville, Florida, United States, 32603"]},{"name":"University of Florida , , , , , , , ,","place":["Gainesville, Florida, United States, 32603"]},{"name":"University of Florida , , , , , , , ,","place":["Gainesville, Florida, United States, 32603"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pedro E.","family":"Cruz","sequence":"additional","affiliation":[{"name":"University of Florida , , , , , , , ,","place":["Gainesville, Florida, United States, 32603"]},{"name":"University of Florida , , , , , , , ,","place":["Gainesville, Florida, United States, 32603"]},{"name":"University of Florida , , , , , , , ,","place":["Gainesville, Florida, United States, 32603"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Awilda M.","family":"Rosario","sequence":"additional","affiliation":[{"name":"University of Florida , , , , , , , ,","place":["Gainesville, Florida, United States, 32603"]},{"name":"University of Florida , , , , , , , ,","place":["Gainesville, Florida, United States, 32603"]},{"name":"University of Florida , , , , , , , ,","place":["Gainesville, Florida, United States, 32603"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas B.","family":"Ladd","sequence":"additional","affiliation":[{"name":"University of Florida , , , , , , , ,","place":["Gainesville, Florida, United States, 32603"]},{"name":"University of Florida , , , , , , , ,","place":["Gainesville, Florida, United States, 32603"]},{"name":"University of Florida , , , , , , , ,","place":["Gainesville, Florida, United States, 32603"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas L.","family":"Kukar","sequence":"additional","affiliation":[{"name":"University of Florida , , , , , , , ,","place":["Gainesville, Florida, United States, 32603"]},{"name":"University of Florida , , , , , , , ,","place":["Gainesville, Florida, United States, 32603"]},{"name":"Emory University School of Medicine , , , ,","place":["Atlanta, Georgia, United States, 30322"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward H.","family":"Koo","sequence":"additional","affiliation":[{"name":"University of Florida , , , , , , , ,","place":["Gainesville, Florida, United States, 32603"]},{"name":"University of Florida , , , , , , , ,","place":["Gainesville, Florida, United States, 32603"]},{"name":"University of California at San Diego , , , ,","place":["La Jolla, California, United States, 92093"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin M.","family":"Felsenstein","sequence":"additional","affiliation":[{"name":"University of Florida , , , , , , , ,","place":["Gainesville, Florida, United States, 32603"]},{"name":"University of Florida , , , , , , , ,","place":["Gainesville, Florida, United States, 32603"]},{"name":"University of Florida , , , , , , , ,","place":["Gainesville, Florida, United States, 32603"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Todd E.","family":"Golde","sequence":"additional","affiliation":[{"name":"University of Florida , , , , , , , ,","place":["Gainesville, Florida, United States, 32603"]},{"name":"University of Florida , , , , , , , ,","place":["Gainesville, Florida, United States, 32603"]},{"name":"University of Florida , , , , , , , ,","place":["Gainesville, Florida, United States, 32603"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2014,3,12]]},"reference":[{"key":"2026090316173197100_cit1","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1126\/science.1072994","article-title":"The amyloid hypothesis\nof Alzheimer\u2019s disease: Progress and problems on the road to\ntherapeutics","volume":"297","author":"Hardy","year":"2002","journal-title":"Science"},{"key":"2026090316173197100_cit2","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1016\/S0925-4439(00)00043-0","article-title":"Biochemical detection\nof A\u03b2\nisoforms: Implications for pathogenesis, diagnosis, and treatment\nof Alzheimer\u2019s disease","volume":"1502","author":"Golde","year":"2000","journal-title":"Biochim. Biophys.\nActa"},{"key":"2026090316173197100_cit3","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1016\/S0928-4257(98)80035-1","article-title":"The role\nof A\u03b242 in Alzheimer\u2019s disease","volume":"92","author":"Younkin","year":"1998","journal-title":"J. Physiol. Paris"},{"key":"2026090316173197100_cit4","doi-asserted-by":"crossref","first-page":"4693","DOI":"10.1021\/bi00069a001","article-title":"The carboxy\nterminus of the \u03b2 amyloid protein is critical for the seeding\nof amyloid formation: Implication for the pathogenesis of Alzheimer\u2019s\ndisease","volume":"32","author":"Jarret","year":"1993","journal-title":"Biochemistry"},{"key":"2026090316173197100_cit5","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/j.neuron.2005.06.030","article-title":"A\u03b242\nis essential for parenchymal\nand vascular amyloid deposition in mice","volume":"47","author":"McGowan","year":"2005","journal-title":"Neuron"},{"key":"2026090316173197100_cit6","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1523\/JNEUROSCI.4849-06.2007","article-title":"A\u03b240\nInhibits Amyloid Deposition In Vivo","volume":"27","author":"Kim","year":"2007","journal-title":"J. Neurosci."},{"key":"2026090316173197100_cit7","doi-asserted-by":"crossref","first-page":"15330","DOI":"10.1074\/jbc.M512574200","article-title":"Wild-type Presenilin\n1 Protects against Alzheimer Disease Mutation-induced Amyloid Pathology","volume":"281","author":"Wang","year":"2006","journal-title":"J. Biol. Chem."},{"key":"2026090316173197100_cit8","doi-asserted-by":"crossref","first-page":"7013","DOI":"10.1074\/jbc.270.13.7013","article-title":"Amyloid \u03b2 Protein (A\u03b2)\nin Alzheimer\u2019s Disease Brain","volume":"270","author":"Gravina","year":"1995","journal-title":"J. Biol.\nChem."},{"key":"2026090316173197100_cit9","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/0896-6273(94)90458-8","article-title":"Visualization of A\u03b242(43)\nand A\u03b240 in senile plaques\nwith end-specific A\u03b2 monoclonals: Evidence that an initially\ndeposited species is A\u03b242(43)","volume":"13","author":"Iwatsubo","year":"1994","journal-title":"Neuron"},{"key":"2026090316173197100_cit10","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1038\/359325a0","article-title":"Isolation and quantification of soluble Alzheimer\u2019s\n\u03b2-peptide from biological fluids","volume":"359","author":"Seubert","year":"1992","journal-title":"Nature"},{"key":"2026090316173197100_cit11","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1186\/alzrt121","article-title":"Overlapping\nprofiles of A\u03b2 peptides in the Alzheimer\u2019s disease and\npathological aging brains","volume":"4","author":"Moore","year":"2012","journal-title":"Alzheimer\u2019s\nRes. Ther."},{"key":"2026090316173197100_cit12","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1111\/j.1471-4159.2006.04211.x","article-title":"Disease\nmodifying therapy for AD","volume":"99","author":"Golde","year":"2006","journal-title":"J. Neurochem."},{"key":"2026090316173197100_cit13","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1038\/nrneurol.2009.218","article-title":"The secretases: Enzymes\nwith therapeutic potential in Alzheimer disease","volume":"6","author":"De Strooper","year":"2010","journal-title":"Nat. Rev. Neurol."},{"key":"2026090316173197100_cit14","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1016\/j.expneurol.2009.07.035","article-title":"Targeting A\u03b2 and tau in Alzheimer\u2019s\ndisease, an early interim report","volume":"223","author":"Golde","year":"2010","journal-title":"Exp. Neurol."},{"key":"2026090316173197100_cit15","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1038\/35102591","article-title":"A subset of NSAIDs\nlower amyloidogenic\nA\u03b242 independently of cyclooxygenase activity","volume":"414","author":"Weggen","year":"2001","journal-title":"Nature"},{"key":"2026090316173197100_cit16","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1172\/JCI18162","article-title":"NSAIDs and enantiomers of flurbiprofen\ntarget \u03b3-secretase and lower A\u03b242 in vivo","volume":"112","author":"Eriksen","year":"2003","journal-title":"J. Clin. Invest."},{"key":"2026090316173197100_cit17","doi-asserted-by":"crossref","first-page":"2898","DOI":"10.1016\/j.bbamem.2013.06.005","article-title":"\u03b3-Secretase\ninhibitors and modulators","volume":"1828","author":"Golde","year":"2013","journal-title":"Biochim. Biophys.\nActa"},{"key":"2026090316173197100_cit18","doi-asserted-by":"crossref","first-page":"47","DOI":"10.2174\/156802608783334042","article-title":"Possible mechanisms\nof action of NSAIDs and related\ncompounds that modulate \u03b3-secretase cleavage","volume":"8","author":"Kukar","year":"2008","journal-title":"Curr. Top. Med. Chem."},{"key":"2026090316173197100_cit19","doi-asserted-by":"crossref","first-page":"1269","DOI":"10.1016\/j.bmcl.2009.11.101","article-title":"Piperazinyl pyrimidine\nderivatives as potent \u03b3-secretase modulators","volume":"20","author":"Rivkin","year":"2010","journal-title":"Bioorg. Med.\nChem. Lett."},{"key":"2026090316173197100_cit20","doi-asserted-by":"crossref","first-page":"17798","DOI":"10.1074\/jbc.M110.103283","article-title":"\u03b2-Amyloid\nPrecursor Protein Mutants Respond to\n\u03b3-Secretase Modulators","volume":"285","author":"Page","year":"2010","journal-title":"J. Biol. Chem."},{"key":"2026090316173197100_cit21","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1186\/alzrt173","article-title":"Efficacy of\nSPI-1865, a novel \u03b3-secretase\nmodulator, in multiple rodent models","volume":"5","author":"Loureiro","year":"2013","journal-title":"Alzheimer\u2019s\nRes. Ther."},{"key":"2026090316173197100_cit22","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1038\/nm1235","article-title":"Diverse compounds\nmimic Alzheimer disease-causing mutations\nby augmenting A\u03b242 production","volume":"11","author":"Kukar","year":"2005","journal-title":"Nat. Med."},{"key":"2026090316173197100_cit23","doi-asserted-by":"crossref","first-page":"1311","DOI":"10.1007\/s00018-008-7462-2","article-title":"Substrate specificity\nof \u03b3-secretase and other\nintramembrane proteases","volume":"65","author":"Beel","year":"2008","journal-title":"Cell. Mol. Life Sci."},{"key":"2026090316173197100_cit24","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/S0896-6273(03)00205-8","article-title":"Aph-1, Pen-2, and Nicastrin with Presenilin Generate\nan Active \u03b3-Secretase Complex","volume":"38","author":"De Strooper","year":"2003","journal-title":"Neuron"},{"key":"2026090316173197100_cit25","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1006\/nbdi.2001.0470","article-title":"Cholesterol-Dependent\n\u03b3-Secretase Activity in Buoyant Cholesterol-Rich Membrane Microdomains","volume":"9","author":"Wahrle","year":"2002","journal-title":"Neurobiol. Dis."},{"key":"2026090316173197100_cit26","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1038\/nm0698-730","article-title":"A detergent-insoluble\nmembrane compartment contains\nA\u03b2 in vivo","volume":"4","author":"Lee","year":"1998","journal-title":"Nat. Med."},{"key":"2026090316173197100_cit27","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1038\/19083","article-title":"A presenilin-1-dependent \u03b3-secretase-like protease mediates\nrelease of Notch intracellular domain","volume":"398","author":"De Strooper","year":"1999","journal-title":"Nature"},{"key":"2026090316173197100_cit28","doi-asserted-by":"crossref","first-page":"30425","DOI":"10.1074\/jbc.C300239200","article-title":"Presenilin-dependent\n\u201c\u03b3-Secretase\u201d\nProcessing of Deleted in Colorectal Cancer (DCC)","volume":"278","author":"Taniguchi","year":"2003","journal-title":"J. Biol. Chem."},{"key":"2026090316173197100_cit29","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1038\/nrm1406","article-title":"\u03b3-Secretase: Proteasome of the membrane?","volume":"5","author":"Kopan","year":"2004","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"2026090316173197100_cit30","doi-asserted-by":"crossref","first-page":"1168","DOI":"10.1046\/j.1471-4159.2001.00516.x","article-title":"The amyloid\nprecursor protein (APP)-cytoplasmic fragment generated by \u03b3-secretase\nis rapidly degraded but distributes partially in a nuclear fraction\nof neurones in culture","volume":"78","author":"Cupers","year":"2001","journal-title":"J. Neurochem."},{"key":"2026090316173197100_cit31","doi-asserted-by":"crossref","first-page":"2261","DOI":"10.1038\/emboj.2012.79","article-title":"The mechanism\nof \u03b3-secretase dysfunction in familial Alzheimer disease","volume":"31","author":"Chavez-Gutierrez","year":"2012","journal-title":"EMBO J."},{"key":"2026090316173197100_cit32","doi-asserted-by":"crossref","first-page":"11914","DOI":"10.1074\/jbc.274.17.11914","article-title":"\u03b3-Secretase, Evidence for Multiple Proteolytic\nActivities and Influence of Membrane Positioning of Substrate on Generation\nof Amyloid \u03b2 Peptides of Varying Length","volume":"274","author":"Murphy","year":"1999","journal-title":"J. Biol. Chem."},{"key":"2026090316173197100_cit33","doi-asserted-by":"crossref","first-page":"39804","DOI":"10.1074\/jbc.M111.274696","article-title":"Lysine 624 of the\nAmyloid Precursor Protein (APP) Is a Critical Determinant of Amyloid\n\u03b2 Peptide Length","volume":"286","author":"Kukar","year":"2011","journal-title":"J. Biol. Chem."},{"key":"2026090316173197100_cit34","doi-asserted-by":"crossref","first-page":"13042","DOI":"10.1523\/JNEUROSCI.2362-09.2009","article-title":"\u03b3-Secretase: Successive Tripeptide\nand Tetrapeptide Release from the Transmembrane Domain of \u03b2-Carboxyl\nTerminal Fragment","volume":"29","author":"Takami","year":"2009","journal-title":"J. Neurosci."},{"key":"2026090316173197100_cit35","doi-asserted-by":"crossref","first-page":"9023","DOI":"10.1021\/bi2007146","article-title":"Dissociation between the Processivity\nand Total Activity of \u03b3-Secretase: Implications for the Mechanism\nof Alzheimer\u2019s Disease-Causing Presenilin Mutations","volume":"50","author":"Quintero-Monzon","year":"2011","journal-title":"Biochemistry"},{"key":"2026090316173197100_cit36","doi-asserted-by":"crossref","first-page":"13532","DOI":"10.1021\/bi049399k","article-title":"Truncated Carboxyl-Terminal Fragments of \u03b2-Amyloid Precursor\nProtein Are Processed to Amyloid \u03b2-Proteins 40 and 42","volume":"43","author":"Funamoto","year":"2004","journal-title":"Biochemistry"},{"key":"2026090316173197100_cit37","doi-asserted-by":"crossref","first-page":"2246","DOI":"10.1038\/ncomms3246","article-title":"Alzheimer\u2019s disease mutations\nin APP but not \u03b3-secretase modulators affect \u03b5-cleavage-dependent\nAICD production","volume":"4","author":"Dimitrov","year":"2013","journal-title":"Nat. Commun."},{"key":"2026090316173197100_cit38","doi-asserted-by":"crossref","first-page":"3276","DOI":"10.1074\/jbc.M113.512921","article-title":"\u03b3-Secretase\nProcessing and Effects of \u03b3-Secretase Inhibitors and Modulators\non Long A\u03b2 Peptides in Cells","volume":"289","author":"Ran","year":"2014","journal-title":"J. Biol.\nChem."},{"key":"2026090316173197100_cit39","doi-asserted-by":"crossref","first-page":"5109","DOI":"10.1074\/jbc.M113.510131","article-title":"\u03b3-Secretase\nassociated with lipid rafts: Multiple\ninteractive pathways in the stepwise processing of \u03b2-carboxyl\nterminal fragment","volume":"289","author":"Matsumura","year":"2013","journal-title":"J. Biol. Chem."},{"key":"2026090316173197100_cit40","doi-asserted-by":"crossref","first-page":"39794","DOI":"10.1074\/jbc.M111.277228","article-title":"Substrate\nSequence Influences \u03b3-Secretase Modulator Activity, Role of\nthe Transmembrane Domain of the Amyloid Precursor Protein","volume":"286","author":"Sagi","year":"2011","journal-title":"J. Biol. Chem."},{"key":"2026090316173197100_cit41","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1111\/jnc.12129","article-title":"Substrate determinants in the C99 juxtamembrane domains differentially\naffect \u03b3-secretase cleavage specificity and modulator pharmacology","volume":"125","author":"Ousson","year":"2013","journal-title":"J. Neurochem."},{"key":"2026090316173197100_cit42","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1074\/jbc.M708754200","article-title":"Generation of A\u03b238\nand A\u03b242 Is Independently and Differentially Affected by Familial\nAlzheimer Disease-associated Presenilin Mutations and \u03b3-Secretase\nModulation","volume":"283","author":"Page","year":"2008","journal-title":"J. Biol. Chem."},{"key":"2026090316173197100_cit43","doi-asserted-by":"crossref","first-page":"1702","DOI":"10.1038\/sj.emboj.7601616","article-title":"GxxxG motifs within the amyloid precursor\nprotein transmembrane\nsequence are critical for the etiology of A\u03b242","volume":"26","author":"Munter","year":"2007","journal-title":"EMBO J."},{"key":"2026090316173197100_cit44","doi-asserted-by":"crossref","first-page":"4903","DOI":"10.1016\/j.bmc.2011.06.062","article-title":"NSAID-derived \u03b3-secretase\nmodulation requires an acidic moiety on the carbazole scaffold","volume":"19","author":"Zall","year":"2011","journal-title":"Bioorg. Med. Chem."},{"key":"2026090316173197100_cit45","doi-asserted-by":"crossref","first-page":"5428","DOI":"10.1016\/j.bmcl.2007.07.044","article-title":"Conversion of the LXR-agonist\nTO-901317: From inverse to normal modulation of \u03b3-secretase\nby addition of a carboxylic acid and a lipophilic anchor","volume":"17","author":"Narlawar","year":"2007","journal-title":"Bioorg. Med. Chem."},{"key":"2026090316173197100_cit46","doi-asserted-by":"crossref","first-page":"14597","DOI":"10.1073\/pnas.1003026107","article-title":"Amyloid \u03b242 peptide (A\u03b242)-lowering compounds\ndirectly bind to A\u03b2 and interfere with amyloid precursor protein\n(APP) transmembrane dimerization","volume":"107","author":"Richter","year":"2010","journal-title":"Proc. Natl.\nAcad. Sci. U.S.A."},{"key":"2026090316173197100_cit47","doi-asserted-by":"crossref","first-page":"925","DOI":"10.1038\/nature07055","article-title":"Substrate-targeting \u03b3-secretase\nmodulators","volume":"453","author":"Kukar","year":"2008","journal-title":"Nature"},{"key":"2026090316173197100_cit48","doi-asserted-by":"crossref","first-page":"738","DOI":"10.1101\/pdb.prot076505","article-title":"PCR-Mediated Site-Directed\nMutagenesis","volume":"2013","author":"Carey","year":"2013","journal-title":"Cold Spring Harbor Protoc."},{"key":"2026090316173197100_cit49","doi-asserted-by":"crossref","first-page":"43343","DOI":"10.1074\/jbc.M108245200","article-title":"Multiple Effects of Aspartate Mutant\nPresenilin 1 on the Processing and Trafficking of Amyloid Precursor\nProtein","volume":"276","author":"Kim","year":"2001","journal-title":"J. Biol. Chem."},{"key":"2026090316173197100_cit50","doi-asserted-by":"crossref","first-page":"35350","DOI":"10.1074\/jbc.M702739200","article-title":"Amyloid \u03b2-Protein\nPrecursor Juxtamembrane Domain Regulates Specificity of \u03b3-Secretase-dependent\nCleavages","volume":"282","author":"Ren","year":"2007","journal-title":"J. Biol. Chem."},{"key":"2026090316173197100_cit51","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.ymeth.2011.04.002","article-title":"A simplified polyethylenimine-mediated\ntransfection process for large-scale and high-throughput applications","volume":"55","author":"Raymond","year":"2011","journal-title":"Methods"},{"key":"2026090316173197100_cit52","doi-asserted-by":"crossref","first-page":"31894","DOI":"10.1074\/jbc.271.50.31894","article-title":"The profile of soluble\namyloid \u03b2 protein in cultured cell media. 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