Trafficking regulation of proteins in Alzheimer's disease

Molecular Neurodegeneration

Volumn 9, Issue 1, 2014, Pages

  Jiang, Shangtong ^a   Li, Yanfang ^a   Zhang, Xian ^a   Bu, Guojun ^a,b   Xu, Huaxi ^a,c   Zhang, Yun Wu ^a  

^a XIAMEN UNIVERSITY   (China)

^b MAYO GRADUATE SCHOOL   (United States)

^c BURNHAM INSTITUTE   (United States)

Author keywords

secretase; secretase; secretase; A Disintegrin and Metalloprotease 10; Alzheimer's disease; Amyloid beta (A4) precursor protein; Beta site APP cleaving enzyme 1; Trafficking

Indexed keywords

ADAM10 ENDOPEPTIDASE; ADAPTOR PROTEIN; ADENOSINE DIPHOSPHATE RIBOSYLATION FACTOR; ALPHA SECRETASE; AMYLOID PRECURSOR PROTEIN; BETA SECRETASE 1; GAMMA SECRETASE; LOW DENSITY LIPOPROTEIN RECEPTOR; PROTEIN; RAB PROTEIN; SORTING NEXIN;

ALZHEIMER DISEASE; CARBOXY TERMINAL SEQUENCE; CELL MIGRATION; ENZYME ACTIVITY; ENZYME REGULATION; HUMAN; NONHUMAN; PROTEIN ASSEMBLY; PROTEIN LOCALIZATION; PROTEIN PROCESSING; PROTEIN STRUCTURE; REGULATORY MECHANISM; REVIEW;

ALZHEIMER DISEASE; HUMANS; PROTEIN TRANSPORT;

EID: 84892377524     PISSN: None     EISSN: 17501326     Source Type: Journal    
DOI: 10.1186/1750-1326-9-6     Document Type: Review

References (195)

1. Biology and pathophysiology of the amyloid precursor protein. Zheng H, Koo EH, Mol Neurodegener 2011 6 27 10.1186/1750-1326-6-27 21527012
2. Neurodegenerative tauopathies. Lee VM, Goedert M, Trojanowski JQ, Annu Rev Neurosci 2001 24 1121 1159 10.1146/annurev.neuro.24.1.1121 11520930
3. The discovery of Alzheimer's disease. Hippius H, Neundorfer G, Dialogues Clin Neurosci 2003 5 101 108 22034141
4. Alzheimer's disease: initial report of the purification and characterization of a novel cerebrovascular amyloid protein. Glenner GG, Wong CW, Biochem Biophys Res Commun 1984 120 885 890 10.1016/S0006-291X(84)80190-4 6375662
5. Amyloid plaque core protein in Alzheimer disease and Down syndrome. Masters CL, Simms G, Weinman NA, Multhaup G, McDonald BL, Beyreuther K, Proc Natl Acad Sci USA 1985 82 4245 4249 10.1073/pnas.82.12.4245 3159021
6. The amyloid hypothesis of Alzheimer's disease: progress and problems on the road to therapeutics. Hardy J, Selkoe DJ, Science 2002 297 353 356 10.1126/science.1072994 12130773
7. Alzheimer's disease: synapses gone cold. Koffie RM, Hyman BT, Spires-Jones TL, Mol Neurodegener 2011 6 63 10.1186/1750-1326-6-63 21871088
8. Alzheimer's disease: the amyloid cascade hypothesis. Hardy JA, Higgins GA, Science 1992 256 184 185 10.1126/science.1566067 1566067
9. Always around, never the same: pathways of amyloid beta induced neurodegeneration throughout the pathogenic cascade of Alzheimer's disease. Hoozemans JJ, Chafekar SM, Baas F, Eikelenboom P, Scheper W, Curr Med Chem 2006 13 2599 2605 10.2174/092986706778201585 17017913
10. APP processing in Alzheimer's disease. Zhang YW, Thompson R, Zhang H, Xu H, Mol Brain 2011 4 3 10.1186/1756-6606-4-3 21214928
11. Identification of a mouse brain cDNA that encodes a protein related to the Alzheimer disease-associated amyloid beta protein precursor. Wasco W, Bupp K, Magendantz M, Gusella JF, Tanzi RE, Solomon F, Proc Natl Acad Sci USA 1992 89 10758 10762 10.1073/pnas.89.22.10758 1279693
12. Isolation and characterization of APLP2 encoding a homologue of the Alzheimer's associated amyloid beta protein precursor. Wasco W, Gurubhagavatula S, Paradis MD, Romano DM, Sisodia SS, Hyman BT, Neve RL, Tanzi RE, Nat Genet 1993 5 95 100 10.1038/ng0993-95 8220435
13. Cell-specific expression of beta-amyloid precursor protein isoform mRNAs and proteins in neurons and astrocytes. de Silva HA R, Jen A, Wickenden C, Jen LS, Wilkinson SL, Patel AJ, Brain Res Mol Brain Res 1997 47 147 156 10.1016/S0169-328X(97)00045-4 9221912
14. Differential splicing of Alzheimer's disease amyloid A4 precursor RNA in rat tissues: PreA4(695) mRNA is predominantly produced in rat and human brain. Kang J, Muller-Hill B, Biochem Biophys Res Commun 1990 166 1192 1200 10.1016/0006-291X(90)90992-V 1689572
15. Generation of Alzheimer beta-amyloid protein in the trans-Golgi network in the apparent absence of vesicle formation. Xu H, Sweeney D, Wang R, Thinakaran G, Lo AC, Sisodia SS, Greengard P, Gandy S, Proc Natl Acad Sci USA 1997 94 3748 3752 10.1073/pnas.94.8.3748 9108049
16. Distinct sites of intracellular production for Alzheimer's disease A beta40/42 amyloid peptides. Hartmann T, Bieger SC, Bruhl B, Tienari PJ, Ida N, Allsop D, Roberts GW, Masters CL, Dotti CG, Unsicker K, Beyreuther K, Nat Med 1997 3 1016 1020 10.1038/nm0997-1016 9288729
17. Endoplasmic reticulum and trans-Golgi network generate distinct populations of Alzheimer beta-amyloid peptides. Greenfield JP, Tsai J, Gouras GK, Hai B, Thinakaran G, Checler F, Sisodia SS, Greengard P, Xu H, Proc Natl Acad Sci USA 1999 96 742 747 10.1073/pnas.96.2.742 9892704
18. Beta-amyloid precursor protein cleavage by a membrane-bound protease. Sisodia SS, Proc Natl Acad Sci USA 1992 89 6075 6079 10.1073/pnas.89.13.6075 1631093
19. Identification of the Alzheimer beta/A4 amyloid precursor protein in clathrin-coated vesicles purified from PC12 cells. Nordstedt C, Caporaso GL, Thyberg J, Gandy SE, Greengard P, J Biol Chem 1993 268 608 612 8416966
20. Morphologic and biochemical analysis of the intracellular trafficking of the Alzheimer beta/A4 amyloid precursor protein. Caporaso GL, Takei K, Gandy SE, Matteoli M, Mundigl O, Greengard P, De Camilli P, J Neurosci 1994 14 3122 3138 8182461
21. Beta-Amyloid peptide and a 3-kDa fragment are derived by distinct cellular mechanisms. Haass C, Hung AY, Schlossmacher MG, Teplow DB, Selkoe DJ, J Biol Chem 1993 268 3021 3024 8428976
22. Normal cellular processing of the beta-amyloid precursor protein results in the secretion of the amyloid beta peptide and related molecules. Haass C, Hung AY, Schlossmacher MG, Oltersdorf T, Teplow DB, Selkoe DJ, Ann N Y Acad Sci 1993 695 109 116 10.1111/j.1749-6632.1993.tb23037.x 8239267
23. Adaptor protein interactions: modulators of amyloid precursor protein metabolism and Alzheimer's disease risk? King GD, Scott Turner R, Exp Neurol 2004 185 208 219 10.1016/j.expneurol.2003.10.011 14736502
24. Mutagenesis identifies new signals for beta-amyloid precursor protein endocytosis, turnover, and the generation of secreted fragments, including Abeta42. Perez RG, Soriano S, Hayes JD, Ostaszewski B, Xia W, Selkoe DJ, Chen X, Stokin GB, Koo EH, J Biol Chem 1999 274 18851 18856 10.1074/jbc.274.27.18851 10383380
25. Structural features of the KPI domain control APP dimerization, trafficking, and processing. Ben Khalifa N, Tyteca D, Marinangeli C, Depuydt M, Collet JF, Courtoy PJ, Renauld JC, Constantinescu S, Octave JN, Kienlen-Campard P, FASEB J 2012 26 855 867 10.1096/fj.11-190207 22085646
26. S655 phosphorylation enhances APP secretory traffic. Vieira SI, Rebelo S, Domingues SC, da Cruz e Silva EF, da Cruz e Silva OA, Mol Cell Biochem 2009 328 145 154 10.1007/s11010-009-0084-7 19381782
27. Retrieval of the Alzheimer's amyloid precursor protein from the endosome to the TGN is S655 phosphorylation state-dependent and retromer-mediated. Vieira SI, Rebelo S, Esselmann H, Wiltfang J, Lah J, Lane R, Small SA, Gandy S, da Cruz ESEF, da Cruz ESOA, Mol Neurodegener 2010 5 40 10.1186/1750-1326-5-40 20937087
28. APP processing is regulated by cytoplasmic phosphorylation. Lee MS, Kao SC, Lemere CA, Xia W, Tseng HC, Zhou Y, Neve R, Ahlijanian MK, Tsai LH, J Cell Biol 2003 163 83 95 10.1083/jcb.200301115 14557249
29. Regulation of amyloid beta-protein precursor by phosphorylation and protein interactions. Suzuki T, Nakaya T, J Biol Chem 2008 283 29633 29637 10.1074/jbc.R800003200 18650433
30. Inhibition of neuronal calcium oscillations by cell surface APP phosphorylated on T668. Santos SF, Tasiaux B, Sindic C, Octave JN, Neurobiol Aging 2011 32 2308 2313 10.1016/j.neurobiolaging.2010.01.006 20122754
31. FBL2 regulates amyloid precursor protein (APP) metabolism by promoting ubiquitination-dependent APP degradation and inhibition of APP endocytosis. Watanabe T, Hikichi Y, Willuweit A, Shintani Y, Horiguchi T, J Neurosci 2012 32 3352 3365 10.1523/JNEUROSCI.5659-11.2012 22399757
32. Ubiquilin-1 regulates amyloid precursor protein maturation and degradation by stimulating K63-linked polyubiquitination of lysine 688. El Ayadi A, Stieren ES, Barral JM, Boehning D, Proc Natl Acad Sci USA 2012 109 13416 13421 10.1073/pnas.1206786109 22847417
33. Ubiquilin 1 modulates amyloid precursor protein trafficking and Abeta secretion. Hiltunen M, Lu A, Thomas AV, Romano DM, Kim M, Jones PB, Xie Z, Kounnas MZ, Wagner SL, Berezovska O, et al. J Biol Chem 2006 281 32240 32253 10.1074/jbc.M603106200 16945923
34. Family-based association between Alzheimer's disease and variants in UBQLN1. Bertram L, Hiltunen M, Parkinson M, Ingelsson M, Lange C, Ramasamy K, Mullin K, Menon R, Sampson AJ, Hsiao MY, et al. N Engl J Med 2005 352 884 894 10.1056/NEJMoa042765 15745979
35. Lipoprotein receptors in the nervous system. Herz J, Bock HH, Annu Rev Biochem 2002 71 405 434 10.1146/annurev.biochem.71.110601.135342 12045102
36. Cellular signalling by lipoprotein receptors. Herz J, Gotthardt M, Willnow TE, Curr Opin Lipidol 2000 11 161 166 10.1097/00041433-200004000-00009 10787178
37. Apolipoprotein E and Alzheimer disease: risk, mechanisms and therapy. Liu CC, Kanekiyo T, Xu H, Bu G, Nat Rev Neurol 2013 9 106 118 10.1038/nrneurol. 2012.263 23296339
38. The YXXL motif, but not the two NPXY motifs, serves as the dominant endocytosis signal for low density lipoprotein receptor-related protein. Li Y, Marzolo MP, van Kerkhof P, Strous GJ, Bu G, J Biol Chem 2000 275 17187 17194 10.1074/jbc.M000490200 10747918
39. Interaction of cytosolic adaptor proteins with neuronal apolipoprotein E receptors and the amyloid precursor protein. Trommsdorff M, Borg JP, Margolis B, Herz J, J Biol Chem 1998 273 33556 33560 10.1074/jbc.273.50.33556 9837937
40. The putative tumor suppressor LRP1B, a novel member of the low density lipoprotein (LDL) receptor family, exhibits both overlapping and distinct properties with the LDL receptor-related protein. Liu CX, Li Y, Obermoeller-McCormick LM, Schwartz AL, Bu G, J Biol Chem 2001 276 28889 28896 10.1074/jbc.M102727200 11384978
41. The low density lipoprotein receptor-related protein 1B retains beta-amyloid precursor protein at the cell surface and reduces amyloid-beta peptide production. Cam JA, Zerbinatti CV, Knisely JM, Hecimovic S, Li Y, Bu G, J Biol Chem 2004 279 29639 29646 10.1074/jbc.M313893200 15126508
42. Apolipoprotein receptor 2 and X11 alpha/beta mediate apolipoprotein E-induced endocytosis of amyloid-beta precursor protein and beta-secretase, leading to amyloid-beta production. He X, Cooley K, Chung CH, Dashti N, Tang J, J Neurosci 2007 27 4052 4060 10.1523/JNEUROSCI.3993-06.2007 17428983
43. DAB1 and Reelin effects on amyloid precursor protein and ApoE receptor 2 trafficking and processing. Hoe HS, Tran TS, Matsuoka Y, Howell BW, Rebeck GW, J Biol Chem 2006 281 35176 35185 10.1074/jbc.M602162200 16951405
44. F-spondin interaction with the apolipoprotein E receptor ApoEr2 affects processing of amyloid precursor protein. Hoe HS, Wessner D, Beffert U, Becker AG, Matsuoka Y, Rebeck GW, Mol Cell Biol 2005 25 9259 9268 10.1128/MCB.25.21. 9259-9268.2005 16227578
45. Intracellular trafficking of LRP9 is dependent on two acidic cluster/dileucine motifs. Boucher R, Larkin H, Brodeur J, Gagnon H, Theriault C, Lavoie C, Histochem Cell Biol 2008 130 315 327 10.1007/s00418-008-0436-5 18461348
46. Identification of acidic dileucine signals in LRP9 that interact with both GGAs and AP-1/AP-2. Doray B, Knisely JM, Wartman L, Bu G, Kornfeld S, Traffic 2008 9 1551 1562 10.1111/j.1600-0854.2008.00786.x 18627575
47. LDLR-related protein 10 (LRP10) regulates amyloid precursor protein (APP) trafficking and processing: evidence for a role in Alzheimer's disease. Brodeur J, Theriault C, Lessard-Beaudoin M, Marcil A, Dahan S, Lavoie C, Mol Neurodegener 2012 7 31 10.1186/1750-1326-7-31 22734645
48. Association between genetic variants in SORL1 and autopsy-confirmed Alzheimer disease. Lee JH, Cheng R, Honig LS, Vonsattel JP, Clark L, Mayeux R, Neurology 2008 70 887 889 10.1212/01.wnl.0000280581.39755.89 17978276
49. Implication of sex and SORL1 variants in italian patients with Alzheimer disease. Cellini E, Tedde A, Bagnoli S, Pradella S, Piacentini S, Sorbi S, Nacmias B, Arch Neurol 2009 66 1260 1266 19822782
50. Meta-analysis of the association between variants in SORL1 and Alzheimer disease. Reitz C, Cheng R, Rogaeva E, Lee JH, Tokuhiro S, Zou F, Bettens K, Sleegers K, Tan EK, Kimura R, et al. Arch Neurol 2011 68 99 106 10.1001/archneurol.2010.346 21220680
51. The neuronal sortilin-related receptor SORL1 is genetically associated with Alzheimer disease. Rogaeva E, Meng Y, Lee JH, Gu Y, Kawarai T, Zou F, Katayama T, Baldwin CT, Cheng R, Hasegawa H, et al. Nat Genet 2007 39 168 177 10.1038/ng1943 17220890
52. Loss of apolipoprotein E receptor LR11 in Alzheimer disease. Scherzer CR, Offe K, Gearing M, Rees HD, Fang G, Heilman CJ, Schaller C, Bujo H, Levey AI, Lah JJ, Arch Neurol 2004 61 1200 1205 15313836
53. Neuronal LR11/sorLA expression is reduced in mild cognitive impairment. Sager KL, Wuu J, Leurgans SE, Rees HD, Gearing M, Mufson EJ, Levey AI, Lah JJ, Ann Neurol 2007 62 640 647 10.1002/ana.21190 17721864
54. Elements of neural adhesion molecules and a yeast vacuolar protein sorting receptor are present in a novel mammalian low density lipoprotein receptor family member. Yamazaki H, Bujo H, Kusunoki J, Seimiya K, Kanaki T, Morisaki N, Schneider WJ, Saito Y, J Biol Chem 1996 271 24761 24768 10.1074/jbc.271.40.24761 8798746
55. Molecular characterization of a novel human hybrid-type receptor that binds the alpha2-macroglobulin receptor-associated protein. Jacobsen L, Madsen P, Moestrup SK, Lund AH, Tommerup N, Nykjaer A, Sottrup-Jensen L, Gliemann J, Petersen CM, J Biol Chem 1996 271 31379 31383 10.1074/jbc.271.49.31379 8940146
56. The lipoprotein receptor LR11 regulates amyloid beta production and amyloid precursor protein traffic in endosomal compartments. Offe K, Dodson SE, Shoemaker JT, Fritz JJ, Gearing M, Levey AI, Lah JJ, J Neurosci 2006 26 1596 1603 10.1523/JNEUROSCI.4946-05.2006 16452683
57. Neuronal sorting protein-related receptor sorLA/LR11 regulates processing of the amyloid precursor protein. Andersen OM, Reiche J, Schmidt V, Gotthardt M, Spoelgen R, Behlke J, von Arnim CA, Breiderhoff T, Jansen P, Wu X, et al. Proc Natl Acad Sci USA 2005 102 13461 13466 10.1073/pnas.0503689102 16174740
58. Sortilin-related receptor with A-type repeats (SORLA) affects the amyloid precursor protein-dependent stimulation of ERK signaling and adult neurogenesis. Rohe M, Carlo AS, Breyhan H, Sporbert A, Militz D, Schmidt V, Wozny C, Harmeier A, Erdmann B, Bales KR, et al. J Biol Chem 2008 283 14826 14834 10.1074/jbc.M710574200 18362153
59. Thousands of rab GTPases for the cell biologist. Diekmann Y, Seixas E, Gouw M, Tavares-Cadete F, Seabra MC, Pereira-Leal JB, PLoS Comput Biol 2011 7 1002217 10.1371/journal.pcbi.1002217 22022256
60. Rab proteins as membrane organizers. Zerial M, McBride H, Nat Rev Mol Cell Biol 2001 2 107 117 10.1038/35052055 11252952
61. The Ras-related GTP-binding protein, Rab1B, regulates early steps in exocytic transport and processing of beta-amyloid precursor protein. Dugan JM, de Wit C, McConlogue L, Maltese WA, J Biol Chem 1995 270 10982 10989 10.1074/jbc.270.18.10982 7738040
62. Differential effects of a Rab6 mutant on secretory versus amyloidogenic processing of Alzheimer's beta-amyloid precursor protein. McConlogue L, Castellano F, de Wit C, Schenk D, Maltese WA, J Biol Chem 1996 271 1343 1348 10.1074/jbc.271.3.1343 8576122
63. Rab8, a small GTPase involved in vesicular traffic between the TGN and the basolateral plasma membrane. Huber LA, Pimplikar S, Parton RG, Virta H, Zerial M, Simons K, J Cell Biol 1993 123 35 45 10.1083/jcb.123.1.35 8408203
64. Protein transport to the dendritic plasma membrane of cultured neurons is regulated by rab8p. Huber LA, de Hoop MJ, Dupree P, Zerial M, Simons K, Dotti C, J Cell Biol 1993 123 47 55 10.1083/jcb.123.1.47 8408204
65. Phox domain interaction with PtdIns(3)P targets the Vam7 t-SNARE to vacuole membranes. Cheever ML, Sato TK, de Beer T, Kutateladze TG, Emr SD, Overduin M, Nat Cell Biol 2001 3 613 618 10.1038/35083000 11433291
66. PtdIns(3)P regulates the neutrophil oxidase complex by binding to the PX domain of p40(phox). Ellson CD, Gobert-Gosse S, Anderson KE, Davidson K, Erdjument-Bromage H, Tempst P, Thuring JW, Cooper MA, Lim ZY, Holmes AB, et al. Nat Cell Biol 2001 3 679 682 10.1038/35083076 11433301
67. A novel sorting nexin modulates endocytic trafficking and alpha-secretase cleavage of the amyloid precursor protein. Schobel S, Neumann S, Hertweck M, Dislich B, Kuhn PH, Kremmer E, Seed B, Baumeister R, Haass C, Lichtenthaler SF, J Biol Chem 2008 283 14257 14268 10.1074/jbc.M801531200 18353773
68. Adaptor protein sorting nexin 17 regulates amyloid precursor protein trafficking and processing in the early endosomes. Lee J, Retamal C, Cuitino L, Caruano-Yzermans A, Shin JE, van Kerkhof P, Marzolo MP, Bu G, J Biol Chem 2008 283 11501 11508 10.1074/jbc.M800642200 18276590
69. The X11/Mint family of adaptor proteins. Rogelj B, Mitchell JC, Miller CC, McLoughlin DM, Brain Res Rev 2006 52 305 315 10.1016/j.brainresrev.2006.04. 005 16764936
70. Regulation of APP-dependent transcription complexes by Mint/X11s: differential functions of Mint isoforms. Biederer T, Cao X, Sudhof TC, Liu X, J Neurosci 2002 22 7340 7351 12196555
71. X11alpha modulates secretory and endocytic trafficking and metabolism of amyloid precursor protein: mutational analysis of the YENPTY sequence. King GD, Perez RG, Steinhilb ML, Gaut JR, Turner RS, Neuroscience 2003 120 143 154 10.1016/S0306-4522(03)00284-7 12849748
72. Intracellular amyloid precursor protein sorting and amyloid-beta secretion are regulated by Src-mediated phosphorylation of Mint2. Chaufty J, Sullivan SE, Ho A, J Neurosci 2012 32 9613 9625 10.1523/JNEUROSCI.0602-12.2012 22787047
73. The X11 proteins, Abeta production and Alzheimer's disease. Miller CC, McLoughlin DM, Lau KF, Tennant ME, Rogelj B, Trends Neurosci 2006 29 280 285 10.1016/j.tins.2006.03.001 16545469
74. Mint3/X11gamma is an ADP-ribosylation factor-dependent adaptor that regulates the traffic of the Alzheimer's Precursor protein from the trans-Golgi network. Shrivastava-Ranjan P, Faundez V, Fang G, Rees H, Lah JJ, Levey AI, Kahn RA, Mol Biol Cell 2008 19 51 64 10.1091/mbc.E07-05-0465 17959829
75. Presenilin-1 regulates intracellular trafficking and cell surface delivery of beta-amyloid precursor protein. Cai D, Leem JY, Greenfield JP, Wang P, Kim BS, Wang R, Lopes KO, Kim SH, Zheng H, Greengard P, et al. J Biol Chem 2003 278 3446 3454 12435726
76. Presenilins interact with Rab11, a small GTPase involved in the regulation of vesicular transport. Dumanchin C, Czech C, Campion D, Cuif MH, Poyot T, Martin C, Charbonnier F, Goud B, Pradier L, Frebourg T, Hum Mol Genet 1999 8 1263 1269 10.1093/hmg/8.7.1263 10369872
77. Alzheimer's presenilin 1 is a putative membrane receptor for rab GDP dissociation inhibitor. Scheper W, Zwart R, Sluijs P, Annaert W, Gool WA, Baas F, Hum Mol Genet 2000 9 303 310 10.1093/hmg/9.2.303 10607841
78. Rab6 membrane association is dependent of Presenilin 1 and cellular phosphorylation events. Scheper W, Zwart R, Baas F, Brain Res Mol Brain Res 2004 122 17 23 10.1016/j.molbrainres.2003.11.013 14992812
79. Presenilin-1 uses phospholipase D1 as a negative regulator of beta-amyloid formation. Cai D, Netzer WJ, Zhong M, Lin Y, Du G, Frohman M, Foster DA, Sisodia SS, Xu H, Gorelick FS, Greengard P, Proc Natl Acad Sci USA 2006 103 1941 1946 10.1073/pnas.0510708103 16449386
80. Phospholipase D1 corrects impaired betaAPP trafficking and neurite outgrowth in familial Alzheimer's disease-linked presenilin-1 mutant neurons. Cai D, Zhong M, Wang R, Netzer WJ, Shields D, Zheng H, Sisodia SS, Foster DA, Gorelick FS, Xu H, Greengard P, Proc Natl Acad Sci USA 2006 103 1936 1940 10.1073/pnas.0510710103 16449385
81. Purification and cloning of amyloid precursor protein beta-secretase from human brain. Sinha S, Anderson JP, Barbour R, Basi GS, Caccavello R, Davis D, Doan M, Dovey HF, Frigon N, Hong J, et al. Nature 1999 402 537 540 10.1038/990114 10591214
82. Beta-secretase cleavage of Alzheimer's amyloid precursor protein by the transmembrane aspartic protease BACE. Vassar R, Bennett BD, Babu-Khan S, Kahn S, Mendiaz EA, Denis P, Teplow DB, Ross S, Amarante P, Loeloff R, et al. Science 1999 286 735 741 10.1126/science.286.5440.735 10531052
83. Membrane-anchored aspartyl protease with Alzheimer's disease beta-secretase activity. Yan R, Bienkowski MJ, Shuck ME, Miao H, Tory MC, Pauley AM, Brashier JR, Stratman NC, Mathews WR, Buhl AE, et al. Nature 1999 402 533 537 10.1038/990107 10591213
84. X11 alpha and x11 beta interact with presenilin-1 via their PDZ domains. Lau KF, McLoughlin DM, Standen C, Miller CC, Mol Cell Neurosci 2000 16 557 565 10.1006/mcne.2000.0898 11083918
85. BACE1 is the major beta-secretase for generation of Abeta peptides by neurons. Cai H, Wang Y, McCarthy D, Wen H, Borchelt DR, Price DL, Wong PC, Nat Neurosci 2001 4 233 234 10.1038/85064 11224536
86. Elevated beta-secretase expression and enzymatic activity detected in sporadic Alzheimer disease. Yang LB, Lindholm K, Yan R, Citron M, Xia W, Yang XL, Beach T, Sue L, Wong P, Price D, et al. Nat Med 2003 9 3 4 10.1038/nm0103-3 12514700
87. Expression and activity of beta-site amyloid precursor protein cleaving enzyme in Alzheimer's disease. Johnston JA, Liu WW, Todd SA, Coulson DT, Murphy S, Irvine GB, Passmore AP, Biochem Soc Trans 2005 33 1096 1100 10.1042/BST20051096 16246054
88. Mice deficient in BACE1, the Alzheimer's beta-secretase, have normal phenotype and abolished beta-amyloid generation. Luo Y, Bolon B, Kahn S, Bennett BD, Babu-Khan S, Denis P, Fan W, Kha H, Zhang J, Gong Y, et al. Nat Neurosci 2001 4 231 232 10.1038/85059 11224535
89. BACE1 gene deletion prevents neuron loss and memory deficits in 5XFAD APP/PS1 transgenic mice. Ohno M, Cole SL, Yasvoina M, Zhao J, Citron M, Berry R, Disterhoft JF, Vassar R, Neurobiol Dis 2007 26 134 145 10.1016/j.nbd.2006.12. 008 17258906
90. BACE1 deficiency rescues memory deficits and cholinergic dysfunction in a mouse model of Alzheimer's disease. Ohno M, Sametsky EA, Younkin LH, Oakley H, Younkin SG, Citron M, Vassar R, Disterhoft JF, Neuron 2004 41 27 33 10.1016/S0896-6273(03)00810-9 14715132
91. Bace1 modulates myelination in the central and peripheral nervous system. Hu X, Hicks CW, He W, Wong P, Macklin WB, Trapp BD, Yan R, Nat Neurosci 2006 9 1520 1525 10.1038/nn1797 17099708
92. Control of peripheral nerve myelination by the beta-secretase BACE1. Willem M, Garratt AN, Novak B, Citron M, Kaufmann S, Rittger A, DeStrooper B, Saftig P, Birchmeier C, Haass C, Science 2006 314 664 666 10.1126/science. 1132341 16990514
93. The cell adhesion protein P-selectin glycoprotein ligand-1 is a substrate for the aspartyl protease BACE1. Lichtenthaler SF, Dominguez DI, Westmeyer GG, Reiss K, Haass C, Saftig P, De Strooper B, Seed B, J Biol Chem 2003 278 48713 48719 10.1074/jbc.M303861200 14507929
94. Alzheimer's beta-secretase, beta-site amyloid precursor protein-cleaving enzyme, is responsible for cleavage secretion of a Golgi-resident sialyltransferase. Kitazume S, Tachida Y, Oka R, Shirotani K, Saido TC, Hashimoto Y, Proc Natl Acad Sci USA 2001 98 13554 13559 10.1073/pnas.241509198 11698669
95. Beta Subunits of voltage-gated sodium channels are novel substrates of beta-site amyloid precursor protein-cleaving enzyme (BACE1) and gamma-secretase. Wong HK, Sakurai T, Oyama F, Kaneko K, Wada K, Miyazaki H, Kurosawa M, De Strooper B, Saftig P, Nukina N, J Biol Chem 2005 280 23009 23017 10.1074/jbc.M414648200 15824102
96. Phenotypic and biochemical analyses of BACE1- and BACE2-deficient mice. Dominguez D, Tournoy J, Hartmann D, Huth T, Cryns K, Deforce S, Serneels L, Camacho IE, Marjaux E, Craessaerts K, et al. J Biol Chem 2005 280 30797 30806 10.1074/jbc.M505249200 15987683
97. BACE1, a major determinant of selective vulnerability of the brain to amyloid-beta amyloidogenesis, is essential for cognitive, emotional, and synaptic functions. Laird FM, Cai H, Savonenko AV, Farah MH, He K, Melnikova T, Wen H, Chiang HC, Xu G, Koliatsos VE, et al. J Neurosci 2005 25 11693 11709 10.1523/JNEUROSCI.2766-05.2005 16354928
98. Partial reduction of BACE1 has dramatic effects on Alzheimer plaque and synaptic pathology in APP Transgenic Mice. McConlogue L, Buttini M, Anderson JP, Brigham EF, Chen KS, Freedman SB, Games D, Johnson-Wood K, Lee M, Zeller M, et al. J Biol Chem 2007 282 26326 26334 10.1074/jbc.M611687200 17616527
99. Characterization of Alzheimer's beta -secretase protein BACE. A pepsin family member with unusual properties. Haniu M, Denis P, Young Y, Mendiaz EA, Fuller J, Hui JO, Bennett BD, Kahn S, Ross S, Burgess T, et al. J Biol Chem 2000 275 21099 21106 10.1074/jbc.M002095200 10887202
100. Post-translational processing of beta-secretase (beta-amyloid-converting enzyme) and its ectodomain shedding. The pro- and transmembrane/cytosolic domains affect its cellular activity and amyloid-beta production. Benjannet S, Elagoz A, Wickham L, Mamarbachi M, Munzer JS, Basak A, Lazure C, Cromlish JA, Sisodia S, Checler F, et al. J Biol Chem 2001 276 10879 10887 10.1074/jbc.M009899200 11152688
101. A furin-like convertase mediates propeptide cleavage of BACE, the Alzheimer's beta -secretase. Bennett BD, Denis P, Haniu M, Teplow DB, Kahn S, Louis JC, Citron M, Vassar R, J Biol Chem 2000 275 37712 37717 10.1074/jbc.M005339200 10956649
102. Processing of beta-secretase by furin and other members of the proprotein convertase family. Creemers JW, Ines Dominguez D, Plets E, Serneels L, Taylor NA, Multhaup G, Craessaerts K, Annaert W, De Strooper B, J Biol Chem 2001 276 4211 4217 10.1074/jbc.M006947200 11071887
103. The pro domain of beta-secretase does not confer strict zymogen-like properties but does assist proper folding of the protease domain. Shi XP, Chen E, Yin KC, Na S, Garsky VM, Lai MT, Li YM, Platchek M, Register RB, Sardana MK, et al. J Biol Chem 2001 276 10366 10373 11266439
104. Phosphorylation regulates intracellular trafficking of beta-secretase. Walter J, Fluhrer R, Hartung B, Willem M, Kaether C, Capell A, Lammich S, Multhaup G, Haass C, J Biol Chem 2001 276 14634 14641 10.1074/jbc.M011116200 11278841
105. Maturation and endosomal targeting of beta-site amyloid precursor protein-cleaving enzyme. The Alzheimer's disease beta-secretase. Huse JT, Pijak DS, Leslie GJ, Lee VM, Doms RW, J Biol Chem 2000 275 33729 33737 10.1074/jbc.M004175200 10924510
106. Beta-secretase processing in the trans-Golgi network preferentially generates truncated amyloid species that accumulate in Alzheimer's disease brain. Huse JT, Liu K, Pijak DS, Carlin D, Lee VM, Doms RW, J Biol Chem 2002 277 16278 16284 10.1074/jbc.M111141200 11847218
107. Activity-induced convergence of APP and BACE-1 in acidic microdomains via an endocytosis-dependent pathway. Das U, Scott DA, Ganguly A, Koo EH, Tang Y, Roy S, Neuron 2013 79 447 460 10.1016/j.neuron.2013.05.035 23931995
108. The GGA proteins: adaptors on the move. Bonifacino JS, Nat Rev Mol Cell Biol 2004 5 23 32 10.1038/nrm1279 14708007
109. A family of ADP-ribosylation factor effectors that can alter membrane transport through the trans-Golgi. Boman AL, Zhang C, Zhu X, Kahn RA, Mol Biol Cell 2000 11 1241 1255 10.1091/mbc.11.4.1241 10749927
110. The GGAs promote ARF-dependent recruitment of clathrin to the TGN. Puertollano R, Randazzo PA, Presley JF, Hartnell LM, Bonifacino JS, Cell 2001 105 93 102 10.1016/S0092-8674(01)00299-9 11301005
111. PI4P promotes the recruitment of the GGA adaptor proteins to the trans-Golgi network and regulates their recognition of the ubiquitin sorting signal. Wang J, Sun HQ, Macia E, Kirchhausen T, Watson H, Bonifacino JS, Yin HL, Mol Biol Cell 2007 18 2646 2655 10.1091/mbc.E06-10-0897 17494868
112. Evolution of mannose 6-phosphate receptors (MPR300 and 46): lysosomal enzyme sorting proteins. Nadimpalli SK, Amancha PK, Curr Protein Pept Sci 2010 11 68 90 10.2174/138920310790274644 20201808
113. Memapsin 2 (beta-secretase) cytosolic domain binds to the VHS domains of GGA1 and GGA2: implications on the endocytosis mechanism of memapsin 2. He X, Chang WP, Koelsch G, Tang J, FEBS Lett 2002 524 183 187 10.1016/S0014-5793(02) 03052-1 12135764
114. GGA proteins mediate the recycling pathway of memapsin 2 (BACE). He X, Li F, Chang WP, Tang J, J Biol Chem 2005 280 11696 11703 10.1074/jbc.M411296200 15615712
115. Demonstration of BACE (beta-secretase) phosphorylation and its interaction with GGA1 in cells by fluorescence-lifetime imaging microscopy. von Arnim CA, Tangredi MM, Peltan ID, Lee BM, Irizarry MC, Kinoshita A, Hyman BT, J Cell Sci 2004 117 5437 5445 10.1242/jcs.01422 15466887
116. GGA1 is expressed in the human brain and affects the generation of amyloid beta-peptide. Wahle T, Thal DR, Sastre M, Rentmeister A, Bogdanovic N, Famulok M, Heneka MT, Walter J, J Neurosci 2006 26 12838 12846 10.1523/JNEUROSCI.1982-06.2006 17151287
117. GGA proteins regulate retrograde transport of BACE1 from endosomes to the trans-Golgi network. Wahle T, Prager K, Raffler N, Haass C, Famulok M, Walter J, Mol Cell Neurosci 2005 29 453 461 10.1016/j.mcn.2005.03.014 15886016
118. GGA1-mediated endocytic traffic of LR11/SorLA alters APP intracellular distribution and amyloid-beta production. Herskowitz JH, Offe K, Deshpande A, Kahn RA, Levey AI, Lah JJ, Mol Biol Cell 2012 23 2645 2657 10.1091/mbc.E12-01- 0014 22621900
119. Trafficking and proteolytic processing of APP. Haass C, Kaether C, Thinakaran G, Sisodia S, Cold Spring Harb Perspect Med 2012 2 006270 22553493
120. Depletion of GGA3 stabilizes BACE and enhances beta-secretase activity. Tesco G, Koh YH, Kang EL, Cameron AN, Das S, Sena-Esteves M, Hiltunen M, Yang SH, Zhong Z, Shen Y, et al. Neuron 2007 54 721 737 10.1016/j.neuron.2007.05.012 17553422
121. Elucidation of the BACE1 regulating factor GGA3 in Alzheimer's disease. Natunen T, Parrado AR, Helisalmi S, Pursiheimo JP, Sarajarvi T, Makinen P, Kurkinen KM, Mullin K, Alafuzoff I, Haapasalo A, et al. J Alzheimers Dis 2013 37 217 232 23970038
122. Ubiquitin regulates GGA3-mediated degradation of BACE1. Kang EL, Cameron AN, Piazza F, Walker KR, Tesco G, J Biol Chem 2010 285 24108 24119 10.1074/jbc.M109.092742 20484053
123. A membrane coat complex essential for endosome-to-Golgi retrograde transport in yeast. Seaman MN, McCaffery JM, Emr SD, J Cell Biol 1998 142 665 681 10.1083/jcb.142.3.665 9700157
124. Diabetes-associated SorCS1 regulates Alzheimer's amyloid-beta metabolism: evidence for involvement of SorL1 and the retromer complex. Lane RF, Raines SM, Steele JW, Ehrlich ME, Lah JA, Small SA, Tanzi RE, Attie AD, Gandy S, J Neurosci 2010 30 13110 13115 10.1523/JNEUROSCI.3872-10.2010 20881129
125. VPS35 haploinsufficiency increases Alzheimer's disease neuropathology. Wen L, Tang FL, Hong Y, Luo SW, Wang CL, He W, Shen C, Jung JU, Xiong F, Lee DH, et al. J Cell Biol 2011 195 765 779 10.1083/jcb.201105109 22105352
126. The location and trafficking routes of the neuronal retromer and its role in amyloid precursor protein transport. Bhalla A, Vetanovetz CP, Morel E, Chamoun Z, Di Paolo G, Small SA, Neurobiol Dis 2012 47 126 134 10.1016/j.nbd.2012.03.030 22516235
127. Model-guided microarray implicates the retromer complex in Alzheimer's disease. Small SA, Kent K, Pierce A, Leung C, Kang MS, Okada H, Honig L, Vonsattel JP, Kim TW, Ann Neurol 2005 58 909 919 10.1002/ana.20667 16315276
128. Proteomic identification of sorting nexin 6 as a negative regulator of BACE1-mediated APP processing. Okada H, Zhang W, Peterhoff C, Hwang JC, Nixon RA, Ryu SH, Kim TW, FASEB J 2010 24 2783 2794 10.1096/fj.09-146357 20354142
129. Sorting nexin 12 interacts with BACE1 and regulates BACE1-mediated APP processing. Zhao Y, Wang Y, Yang J, Wang X, Zhang X, Zhang YW, Mol Neurodegener 2012 7 30 10.1186/1750-1326-7-30 22709416
130. ADP ribosylation factor 6 (ARF6) controls amyloid precursor protein (APP) processing by mediating the endosomal sorting of BACE1. Sannerud R, Declerck I, Peric A, Raemaekers T, Menendez G, Zhou L, Veerle B, Coen K, Munck S, De Strooper B, et al. Proc Natl Acad Sci USA 2011 108 559 E568 10.1073/pnas. 1100745108 21825135
131. CutA divalent cation tolerance homolog (Escherichia coli) (CUTA) regulates beta-cleavage of beta-amyloid precursor protein (APP) through interacting with beta-site APP cleaving protein 1 (BACE1). Zhao Y, Wang Y, Hu J, Zhang X, Zhang YW, J Biol Chem 2012 287 11141 11150 10.1074/jbc.M111.330209 22351782
132. Reticulons RTN3 and RTN4-B/C interact with BACE1 and inhibit its ability to produce amyloid beta-protein. Murayama KS, Kametani F, Saito S, Kume H, Akiyama H, Araki W, Eur J Neurosci 2006 24 1237 1244 10.1111/j.1460-9568.2006. 05005.x 16965550
133. The role of reticulons in neurodegenerative diseases. Chiurchiu V, Maccarrone M, Orlacchio A, Neuromolecular Med 2013 doi:10.1007/s12017-013-8271-9
134. Reduced amyloid deposition in mice overexpressing RTN3 is adversely
135. Reticulon family members modulate BACE1 activity and amyloid-beta peptide generation. He W, Lu Y, Qahwash I, Hu XY, Chang A, Yan R, Nat Med 2004 10 959 965 10.1038/nm1088 15286784
136. Alzheimer precursor protein interaction with the Nogo-66 receptor reduces amyloid-beta plaque deposition. Park JH, Gimbel DA, GrandPre T, Lee JK, Kim JE, Li W, Lee DH, Strittmatter SM, J Neurosci 2006 26 1386 1395 10.1523/JNEUROSCI.3291-05.2006 16452662
137. Interaction between amyloid precursor protein and Nogo receptors regulates amyloid deposition. Zhou X, Hu X, He W, Tang X, Shi Q, Zhang Z, Yan R, FASEB J 2011 25 3146 3156 10.1096/fj.11-184325 21670066
138. The presenilins in Alzheimer's disease-proteolysis holds the key. Haass C, De Strooper B, Science 1999 286 916 919 10.1126/science.286.5441.916 10542139
139. Regulation of tyrosinase trafficking and processing by presenilins: partial loss of function by familial Alzheimer's disease mutation. Wang R, Tang P, Wang P, Boissy RE, Zheng H, Proc Natl Acad Sci USA 2006 103 353 358 10.1073/pnas.0509822102 16384915
140. Gamma-secretase is a membrane protein complex comprised of presenilin, nicastrin, Aph-1, and Pen-2. Kimberly WT, LaVoie MJ, Ostaszewski BL, Ye W, Wolfe MS, Selkoe DJ, Proc Natl Acad Sci USA 2003 100 6382 6387 10.1073/pnas. 1037392100 12740439
141. The role of presenilin cofactors in the gamma-secretase complex. Takasugi N, Tomita T, Hayashi I, Tsuruoka M, Niimura M, Takahashi Y, Thinakaran G, Iwatsubo T, Nature 2003 422 438 441 10.1038/nature01506 12660785
142. The ins and outs of presenilin 1 membrane topology. Kim J, Schekman R, Proc Natl Acad Sci USA 2004 101 905 906 10.1073/pnas.0307297101 14732690
143. Two transmembrane aspartates in presenilin-1 required for presenilin endoproteolysis and gamma-secretase activity. Wolfe MS, Xia W, Ostaszewski BL, Diehl TS, Kimberly WT, Selkoe DJ, Nature 1999 398 513 517 10.1038/19077 10206644
144. Nicastrin functions as a gamma-secretase-substrate receptor. Shah S, Lee SF, Tabuchi K, Hao YH, Yu C, LaPlant Q, Ball H, Dann CE 3rd, Sudhof T, Yu G, Cell 2005 122 435 447 10.1016/j.cell.2005.05.022 16096062
145. PEN-2 and APH-1 coordinately regulate proteolytic processing of presenilin 1. Luo WJ, Wang H, Li H, Kim BS, Shah S, Lee HJ, Thinakaran G, Kim TW, Yu G, Xu H, J Biol Chem 2003 278 7850 7854 10.1074/jbc.C200648200 12522139
146. Activation and intrinsic {gamma}-secretase activity of presenilin 1. Ahn K, Shelton CC, Tian Y, Zhang X, Gilchrist ML, Sisodia SS, Li YM, Proc Natl Acad Sci USA 2010 107 21435 21440 10.1073/pnas.1013246107 21115843
147. Assembly of the presenilin gamma-/epsilon-secretase complex. St George-Hyslop P, Fraser PE, J Neurochem 2012 120 Suppl 1 84 88 22122073
148. The role of the endosomal/lysosomal system in amyloid-beta production and the pathophysiology of Alzheimer's disease: reexamining the spatial paradox from a lysosomal perspective. Pasternak SH, Callahan JW, Mahuran DJ, J Alzheimers Dis 2004 6 53 65 15004328
149. Amyloid precursor protein and Notch intracellular domains are generated after transport of their precursors to the cell surface. Kaether C, Schmitt S, Willem M, Haass C, Traffic 2006 7 408 415 10.1111/j.1600-0854.2006.00396.x 16536739
150. Autophagy, amyloidogenesis and Alzheimer disease. Nixon RA, J Cell Sci 2007 120 4081 4091 10.1242/jcs.019265 18032783
151. Assembly, maturation, and trafficking of the gamma-secretase complex in Alzheimer's disease. Dries DR, Yu G, Curr Alzheimer Res 2008 5 132 146 10.2174/156720508783954695 18393798
152. Pathological and physiological functions of presenilins. Vetrivel KS, Zhang YW, Xu H, Thinakaran G, Mol Neurodegener 2006 1 4 10.1186/1750-1326-1-4 16930451
153. Intracellular trafficking of presenilin 1 is regulated by beta-amyloid precursor protein and phospholipase D1. Liu Y, Zhang YW, Wang X, Zhang H, You X, Liao FF, Xu H, J Biol Chem 2009 284 12145 12152 10.1074/jbc.M808497200 19276086
154. Increased App expression in a mouse model of Down's syndrome disrupts NGF transport and causes cholinergic neuron degeneration. Salehi A, Delcroix JD, Belichenko PV, Zhan K, Wu C, Valletta JS, Takimoto-Kimura R, Kleschevnikov AM, Sambamurti K, Chung PP, et al. Neuron 2006 51 29 42 10.1016/j.neuron.2006.05.022 16815330
155. Kinesin-mediated axonal transport of a membrane compartment containing beta-secretase and presenilin-1 requires APP. Kamal A, Almenar-Queralt A, LeBlanc JF, Roberts EA, Goldstein LS, Nature 2001 414 643 648 10.1038/414643a 11740561
156. Arc/Arg3.1 regulates an endosomal pathway essential for activity-dependent beta-amyloid generation. Wu J, Petralia RS, Kurushima H, Patel H, Jung MY, Volk L, Chowdhury S, Shepherd JD, Dehoff M, Li Y, et al. Cell 2011 147 615 628 10.1016/j.cell.2011.09.036 22036569
157. Activation of beta2-adrenergic receptor stimulates gamma-secretase activity and accelerates amyloid plaque formation. Ni Y, Zhao X, Bao G, Zou L, Teng L, Wang Z, Song M, Xiong J, Bai Y, Pei G, Nat Med 2006 12 1390 1396 17115048
158. The orphan G protein-coupled receptor 3 modulates amyloid-beta peptide generation in neurons. Thathiah A, Spittaels K, Hoffmann M, Staes M, Cohen A, Horre K, Vanbrabant M, Coun F, Baekelandt V, Delacourte A, et al. Science 2009 323 946 951 10.1126/science.1160649 19213921
159. Beta-arrestin 2 regulates Abeta generation and gamma-secretase activity in Alzheimer's disease. Thathiah A, Horre K, Snellinx A, Vandewyer E, Huang Y, Ciesielska M, De Kloe G, Munck S, De Strooper B, Nat Med 2013 19 43 49 23202293
160. G protein-coupled receptors. III. New roles for receptor kinases and beta-arrestins in receptor signaling and desensitization. Lefkowitz RJ, J Biol Chem 1998 273 18677 18680 10.1074/jbc.273.30.18677 9668034
161. Gpr3 stimulates Abeta production via interactions with APP and beta-arrestin2. Nelson CD, Sheng M, PLoS One 2013 8 74680 10.1371/journal.pone. 0074680 24069330
162. Beta-arrestin1 regulates gamma-secretase complex assembly and modulates amyloid-beta pathology. Liu X, Zhao X, Zeng X, Bossers K, Swaab DF, Zhao J, Pei G, Cell Res 2013 23 351 365 10.1038/cr.2012.167 23208420
163. Rer1p competes with APH-1 for binding to nicastrin and regulates gamma-secretase complex assembly in the early secretory pathway. Spasic D, Raemaekers T, Dillen K, Declerck I, Baert V, Serneels L, Fullekrug J, Annaert W, J Cell Biol 2007 176 629 640 10.1083/jcb.200609180 17325205
164. Endoplasmic reticulum retention of the gamma-secretase complex component Pen2 by Rer1. Kaether C, Scheuermann J, Fassler M, Zilow S, Shirotani K, Valkova C, Novak B, Kacmar S, Steiner H, Haass C, EMBO Rep 2007 8 743 748 10.1038/sj.embor.7401027 17668005
165. Retention in endoplasmic reticulum 1 (RER1) modulates amyloid-beta (Abeta) production by altering trafficking of gamma-secretase and amyloid precursor protein (APP). Park HJ, Shabashvili D, Nekorchuk MD, Shyqyriu E, Jung JI, Ladd TB, Moore BD, Felsenstein KM, Golde TE, Kim SH, J Biol Chem 2012 287 40629 40640 10.1074/jbc.M112.418442 23043097
166. ABCA2 is a strong genetic risk factor for early-onset Alzheimer's disease. Mace S, Cousin E, Ricard S, Genin E, Spanakis E, Lafargue-Soubigou C, Genin B, Fournel R, Roche S, Haussy G, et al. Neurobiol Dis 2005 18 119 125 10.1016/j.nbd.2004.09.011 15649702
167. Ethnicity-dependent genetic association of ABCA2 with sporadic Alzheimer's disease. Wollmer MA, Kapaki E, Hersberger M, Muntwyler J, Brunner F, Tsolaki M, Akatsu H, Kosaka K, Michikawa M, Molyva D, et al. Am J Med Genet B Neuropsychiatr Genet 2006 141B 534 536 10.1002/ajmg.b.30345 16752360
168. Down-regulation of the ATP-binding cassette transporter 2 (Abca2) reduces amyloid-beta production by altering Nicastrin maturation and intracellular localization. Michaki V, Guix FX, Vennekens K, Munck S, Dingwall C, Davis JB, Townsend DM, Tew KD, Feiguin F, De Strooper B, et al. J Biol Chem 2012 287 1100 1111 10.1074/jbc.M111.288258 22086926
169. P2Y2 nucleotide receptors enhance alpha-secretase-dependent amyloid precursor protein processing. Camden JM, Schrader AM, Camden RE, Gonzalez FA, Erb L, Seye CI, Weisman GA, J Biol Chem 2005 280 18696 18702 10.1074/jbc.M500219200 15778502
170. The neuropeptide PACAP38 induces dendritic spine remodeling through ADAM10-N-cadherin signaling pathway. Gardoni F, Saraceno C, Malinverno M, Marcello E, Verpelli C, Sala C, Di Luca M, J Cell Sci 2012 125 1401 1406 10.1242/jcs.097576 22328515
171. Muscarinic regulation of Alzheimer's disease amyloid precursor protein secretion and amyloid beta-protein production in human neuronal NT2N cells. Wolf BA, Wertkin AM, Jolly YC, Yasuda RP, Wolfe BB, Konrad RJ, Manning D, Ravi S, Williamson JR, Lee VM, J Biol Chem 1995 270 4916 4922 10.1074/jbc.270.9.4916 7876266
172. M1 muscarinic agonists can modulate some of the hallmarks in Alzheimer's disease: implications in future therapy. Fisher A, Pittel Z, Haring R, Bar-Ner N, Kliger-Spatz M, Natan N, Egozi I, Sonego H, Marcovitch I, Brandeis R, J Mol Neurosci 2003 20 349 356 10.1385/JMN:20:3:349 14501019
173. ADAM proteases: protective role in Alzheimer's and prion diseases? Vincent B, Curr Alzheimer Res 2004 1 165 174 10.2174/1567205043332072 15975064
174. Adam meets Eph: an ADAM substrate recognition module acts as a molecular switch for ephrin cleavage in trans. Janes PW, Saha N, Barton WA, Kolev MV, Wimmer-Kleikamp SH, Nievergall E, Blobel CP, Himanen JP, Lackmann M, Nikolov DB, Cell 2005 123 291 304 10.1016/j.cell.2005.08.014 16239146
175. A novel proteolytic cleavage involved in Notch signaling: the role of the disintegrin-metalloprotease TACE. Brou C, Logeat F, Gupta N, Bessia C, LeBail O, Doedens JR, Cumano A, Roux P, Black RA, Israel A, Mol Cell 2000 5 207 216 10.1016/S1097-2765(00)80417-7 10882063
176. MDC9, a widely expressed cellular disintegrin containing cytoplasmic SH3 ligand domains. Weskamp G, Kratzschmar J, Reid MS, Blobel CP, J Cell Biol 1996 132 717 726 10.1083/jcb.132.4.717 8647900
177. A metalloproteinase disintegrin that releases tumour-necrosis factor-alpha from cells. Black RA, Rauch CT, Kozlosky CJ, Peschon JJ, Slack JL, Wolfson MF, Castner BJ, Stocking KL, Reddy P, Srinivasan S, et al. Nature 1997 385 729 733 10.1038/385729a0 9034190
178. Coordinated expression of beta-amyloid precursor protein and the putative beta-secretase BACE and alpha-secretase ADAM10 in mouse and human brain. Marcinkiewicz M, Seidah NG, J Neurochem 2000 75 2133 2143 11032903
179. The disintegrin/metalloproteinase ADAM10 is essential for the establishment of the brain cortex. Jorissen E, Prox J, Bernreuther C, Weber S, Schwanbeck R, Serneels L, Snellinx A, Craessaerts K, Thathiah A, Tesseur I, et al. J Neurosci 2010 30 4833 4844 10.1523/JNEUROSCI.5221-09.2010 20371803
180. ADAMs family members as amyloid precursor protein alpha-secretases. Allinson TM, Parkin ET, Turner AJ, Hooper NM, J Neurosci Res 2003 74 342 352 10.1002/jnr.10737 14598310
181. ADAM10 is the physiologically relevant, constitutive alpha-secretase of the amyloid precursor protein in primary neurons. Kuhn PH, Wang H, Dislich B, Colombo A, Zeitschel U, Ellwart JW, Kremmer E, Rossner S, Lichtenthaler SF, EMBO J 2010 29 3020 3032 10.1038/emboj.2010.167 20676056
182. Alpha- and beta-secretase: profound changes in Alzheimer's disease. Tyler SJ, Dawbarn D, Wilcock GK, Allen SJ, Biochem Biophys Res Commun 2002 299 373 376 10.1016/S0006-291X(02)02635-9 12445809
183. [Alpha]-Secretase ADAM10 as well as [alpha]APPs is reduced in platelets and CSF of Alzheimer disease patients. Colciaghi F, Borroni B, Pastorino L, Marcello E, Zimmermann M, Cattabeni F, Padovani A, Di Luca M, Mol Med 2002 8 67 74 12080182
184. Metalloprotease-dependent protransforming growth factor-alpha ectodomain shedding in the absence of tumor necrosis factor-alpha-converting enzyme. Merlos-Suarez A, Ruiz-Paz S, Baselga J, Arribas J, J Biol Chem 2001 276 48510 48517 11600492
185. Constitutive and regulated alpha-secretase cleavage of Alzheimer's amyloid precursor protein by a disintegrin metalloprotease. Lammich S, Kojro E, Postina R, Gilbert S, Pfeiffer R, Jasionowski M, Haass C, Fahrenholz F, Proc Natl Acad Sci USA 1999 96 3922 3927 10.1073/pnas.96.7.3922 10097139
186. Two independent targeting signals in the cytoplasmic domain determine trans-Golgi network localization and endosomal trafficking of the proprotein convertase furin. Schafer W, Stroh A, Berghofer S, Seiler J, Vey M, Kruse ML, Kern HF, Klenk HD, Garten W, EMBO J 1995 14 2424 2435 7781597
187. Furin and proprotein convertase 7 (PC7)/lymphoma PC endogenously expressed in rat liver can be resolved into distinct post-Golgi compartments. Wouters S, Leruth M, Decroly E, Vandenbranden M, Creemers JW, van de Loo JW, Ruysschaert JM, Courtoy PJ, Biochem J 1998 336 Pt 2 311 316 9820806
188. Cleavage of Alzheimer's amyloid precursor protein by alpha-secretase occurs at the surface of neuronal cells. Parvathy S, Hussain I, Karran EH, Turner AJ, Hooper NM, Biochemistry 1999 38 9728 9734 10.1021/bi9906827 10423252
189. Protein kinase C-dependent alpha-secretase competes with beta-secretase for cleavage of amyloid-beta precursor protein in the trans-golgi network. Skovronsky DM, Moore DB, Milla ME, Doms RW, Lee VM, J Biol Chem 2000 275 2568 2575 10.1074/jbc.275.4.2568 10644715
190. Shedding light on ADAM metalloproteinases. Huovila AP, Turner AJ, Pelto-Huikko M, Karkkainen I, Ortiz RM, Trends Biochem Sci 2005 30 413 422 10.1016/j.tibs.2005.05.006 15949939
191. Alpha-secretase in Alzheimer's disease: molecular identity, regulation and therapeutic potential. Lichtenthaler SF, J Neurochem 2011 116 10 21 10.1111/j.1471-4159.2010.07081.x 21044078
192. An arginine stretch limits ADAM10 exit from the endoplasmic reticulum. Marcello E, Gardoni F, Di Luca M, Perez-Otano I, J Biol Chem 2010 285 10376 10384 10.1074/jbc.M109.055947 20100836
193. Synapse-associated protein-97 mediates alpha-secretase ADAM10 trafficking and promotes its activity. Marcello E, Gardoni F, Mauceri D, Romorini S, Jeromin A, Epis R, Borroni B, Cattabeni F, Sala C, Padovani A, Di Luca M, J Neurosci 2007 27 1682 1691 10.1523/JNEUROSCI.3439-06.2007 17301176
194. SAP97-mediated local trafficking is altered in Alzheimer disease patients' hippocampus. Marcello E, Epis R, Saraceno C, Gardoni F, Borroni B, Cattabeni F, Padovani A, Di Luca M, Neurobiol Aging 2012 33 422 e421-410
195. Endocytosis of synaptic ADAM10 in neuronal plasticity and Alzheimer's disease. Marcello E, Saraceno C, Musardo S, Vara H, de la Fuente AG, Pelucchi S, Di Marino D, Borroni B, Tramontano A, Perez-Otano I, et al. J Clin Invest 2013 123 2523 2538 10.1172/JCI65401 23676497