Activation of the α-secretase processing of AβPP as a therapeutic approach in alzheimer's disease

Journal of Alzheimer's Disease

Volumn 24, Issue SUPPL. 2, 2011, Pages 75-94

  Vincent, Bruno ^a,b   Govitrapong, Piyarat ^a  

^a MAHIDOL UNIVERSITY   (Thailand)

^b UNIVERSITÉ CÔTE D'AZUR   (France)

Author keywords

Alzheimer's disease; amyloid peptide; A PP; disintegrins; sA PP ; Secretase

Indexed keywords

1,3 CAPRYLOYL 2 ARACHIDONOYLGLYCEROL; 4 AMINOPHENYLMERCURIC ACETATE; ACTIVATION INDUCED CYTIDINE DEAMINASE; ADAM10 ENDOPEPTIDASE; ADAM15 ENDOPEPTIDASE; ADAM17 ENDOPEPTIDASE; ADAM9 ENDOPEPTIDASE; ALPHA SECRETASE; ALPHA SECRETASE ACTIVATOR; AMYLOID BETA PROTEIN; AMYLOID PRECURSOR PROTEIN; BETA SECRETASE; CRYPTOTANSHINONE; DISINTEGRIN; ENZYME ACTIVATOR; EPIGALLOCATECHIN GALLATE; GAMMA SECRETASE; GINKGO BILOBA EXTRACT; GLYCEROL DERIVATIVE; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; LEVACECARNINE; NATURAL PRODUCT; PROTEINASE; RECOMBINANT AMYLOID PRECURSOR PROTEIN ALPHA; RECOMBINANT PROTEIN; SELEGILINE; SQUAMOSIDE DERIVATIVE; STREPTOLYSIN O; UNCLASSIFIED DRUG; UNINDEXED DRUG;

ALZHEIMER DISEASE; DRUG TARGETING; ENZYME ACTIVATION; ENZYME DEGRADATION; ENZYME INHIBITION; HUMAN; NONHUMAN; PRIORITY JOURNAL; PROTEIN CLEAVAGE; PROTEIN DOMAIN; PROTEIN PROCESSING; PROTEIN SECRETION; REVIEW; SENILE PLAQUE; TRANSCRIPTION REGULATION; UPREGULATION;

EID: 79955655453     PISSN: 13872877     EISSN: None     Source Type: Journal    
DOI: 10.3233/JAD-2011-110218     Document Type: Review

References (178)

1. Brookmeyer R, Johnson E, Ziegler-Graham K, Arrighi HM (2007) Forecasting the global burden of Alzheimer's dis-ease. Alzheimers Dement 3, 186-191. (Pubitemid 46825511)
2. Glenner GG, Wong CW (1984) Alzheimer's disease: initial report of purification and characterization of a novel cerebrovascular amyloid protein. Biochem Biophys Res Commun 120, 885-890. (Pubitemid 14104991)
3. Kang J, Lemaire HG, Unterbeck A, Salbaum JM, Masters CL, Grzeschik KH, Multhaup G, Beyreuther K, Müller-Hill B (1987) The precursor of Alzheimer's disease amyloid A4 protein resembles a cell-surface receptor. Nature 325, 733-736. (Pubitemid 17054046)
4. Destrooper B (2010) Proteases and proteolysis in Alzheimer disease: a multifactorial view on the disease process. Physiol Rev 90, 465-494.
5. Schubert D, Schroeder R, LaCorbiere M, Saitoh T, Cole G (1988) Amyloid β protein precursor is possibly a heparan sulfate proteoglycan core protein. Science 241, 223-226.
6. Esch FS, Keim PS, Beattie EC, Blacher RW, Culwell AR, Oltersdorf T, McClure D, Ward PJ (1990) Cleavage of amy-loid β peptide during constitutive processing of its pre-cursor. Science 248, 1122-1128.
7. Anderson JP, Esch FS, Keim PS, Sambamurti K, Lieberburg I, Robakis NK (1991) Exact cleavage site of Alzheimer amy-loid precursor in neuronal PC-12 cells. Neurosci Lett 128, 126-128.
8. Wang R, Meschia JF, Cotter RJ, Sisodia SS (1991) Secretion of the β/A4 amyloid precursor protein. J Biol Chem 266, 16960-16964.
9. Sisodia SS (1992) β-amyloid precursor protein cleavage by a membrane-bound protease. Proc Natl Acad Sci USA 89, 6075-6079.
10. Sahasrabudhe SR, Spruyt MA, Muenkel HA, Blume AJ, Vitek MP, Jacobsen JS (1992) Release of amino-terminal fragments from amyloid precursor protein reporter and mutated derivatives in cultured cells. J Biol Chem 267, 25602-25608.
11. Haass C, Koo EH, Mellon A, Hung AY, Selkoe DJ (1992) Targeting of cell surface β-amyloid precursor protein to lysosomes: alternative processing into amyloid-bearing fragments. Nature 357, 500-503.
12. Nordstedt C, Caporaso GL, Thyberg J, Gandy SE, Greengard P (1993) Identification of the Alzheimer β/A4 amyloid precursor protein in clathrin-coated vesicles puri-fied from PC12 cells. J Biol Chem 268, 608-612. (Pubitemid 23021365)
13. Koo EH, Squazzo SL (1994) Evidence that production and release of amyloid β-protein involves the endocytic path-way. J Biol Chem 269, 17386-17389. (Pubitemid 24218009)
14. Parvathy S, Hussain I, Karran EH, Turner AJ, Hooper NM (1999) Cleavage of Alzheimer's amyloid precursor protein by α-secretase occurs at the surface of neuronal cells. Bio-chemistry 38, 9728-9734.
15. Sambamurti K, Shioi J, Anderson JP, Papolla MA, Robakis N (1992) Evidence for intracellular cleavage of the Alzhei-mer's amyloid precursor in PC12 cells. J Neurosci Res 33, 319-329.
16. Kuentzel SL, Ali SM, Altman RA, Greenberg BD, Raub TJ (1993) The Alzheimerβ-amyloidproteinprecursor/protease nexin-II is cleaved by secretase in a trans-Golgi secretory compartment in human neuroglioma cells. Biochem J 295, 367-378. (Pubitemid 23315173)
17. De Strooper B, Umans L, Van Leuven F, Van der Berghe H (1993) Study of the synthesis and secretion of normal and artificial mutants of murine amyloid precursor protein (APP): cleavage of APP occurs in a late compartment of the default secretion pathway. J Cell Biol 121, 295-304. (Pubitemid 23110874)
18. Tomita S, Kirino Y, Suzuki T (1997) Cleavage of Alzhei-mer's amyloid precursor protein (APP) by secretases occurs after O-glycosylation of APP in the protein secretory path-way. J Biol Chem 273, 6277-6284.
19. Shin RW, Saido TC, Maeda M, Kitamoto T (2005) Novel α-secretase cleavage of Alzheimer's amyloid β precursor protein in the endoplasmic reticulum of COS7 cells. Neu-rosciLett 376, 14-19. (Pubitemid 40202929)
20. Maruyama K, Kametani F, Usami M, Yamao-Harigaya W, Tanaka K (1991) Secretase, Alzheimer amyloid protein pre-cursor secreting enzyme is not sequence specific. Biochem Biophys Res Commun 179, 1670-1676.
21. McDermott JR, Gibson AM (1991) The processing of Alzheimer A4/β-amyloid protein precursor: identification of a human brain metallopeptidase which cleaves-lys-leu-in a model peptide. Biochem Biophys Res Commun 179, 1148-1154.
22. Allsop D, Yamamoto T, Kametani F, Miyazaki N, Ishii T (1991) Alzheimer amyloid β/A4 peptide binding sites and a possible "APP secretase" activity associated with rat brain cortical membranes. Brain Res 551, 1-9.
23. Roberts SB, Ripellino JA, Ingalls KM, Robakis NK, Felsenstein KM (1994) Non-amyloidogenic cleavage ofthe β-amyloid precursor protein by an integral membrane met-alloendopeptidase. J Biol Chem269, 3111-3116.
24. Buxbaum JD, Gandy SE, Cicchetti P, Ehrlich ME, Czernik AJ, Fracasso RP, Ramabhadran TV, Unterbeck AJ, Green-gard P (1990) Processing of Alzheimer beta/A4 amyloid precursor protein: modulationby agents that regulate protein phosphorylation. Proc Natl Acad Sci USA 87, 6003-6006.
25. Caporaso GL, Gandy SE, Buxbaum JD, Ramabhadran TV, Greengard P (1992) Protein phosphorylation regulates secretion of Alzheimer beta/A4 amyloid precursor protein. Proc Natl Acad Sci USA 89, 3055-3059.
26. Checler F (1995) Processing ofthe β-amyloidprecursorpro-tein and its regulation in Alzheimer's disease. J Neurochem 65, 1431-1444.
27. Tagawa K, Kunishita T, Maruyama K, Yoshizawa K, Kominami E, Tsuchiya T, Suzuki K, Tabira T, Sugita H, Ishiura S (1991) Alzheimer's disease amyloid β-clipping enzyme (APP secretase): identification, purification, and characterization of the enzyme. Biochem Biophys Res Com-mun 177, 377-387.
28. Small DH, Moir RD, Fuller SJ, Michaelson S, Bush AI, Li QX, Milward E, Hilbich C, Weidemann A, Beyreuther K, Masters CL (1991) A protease activity associated with acetylcholinesterase releases the membrane-bound form of the amyloid protein precursor of Alzheimer's disease. Bio-chemistry30, 10795-10799.
29. Kojima I, Omori M (1992) Two-way cleavage of β-amyloid protein precursor by multicatalytic proteinase. FEBS Lett 304, 57-60.
30. Miyazaki K, Hasegawa M, Funahashi K, Umeda M (1993) A metalloprotease inhibitor domain in Alzheimer amyloid protein precursor. Nature 362, 839-841. (Pubitemid 23132158)
31. Schönlein C, Löffler J, Huber G (1994) Purification and characterization of a novel metalloprotease from human brain with the ability to cleave substrates derived from the N-terminus of β-amyloid protein. Biochem Biophys Res Commun 201, 45-53. (Pubitemid 24213692)
32. Marks N, Berg MJ, Chi LM, Choi J, Durrie R, Swistok J, Makofske RC, Danho W, Sapirstein VS (1994) Hydrolysis of amyloid precursor protein-derived peptides by cysteine proteinases andextracts ofratbrainclathrin-coatedvesicles. Peptides15, 175-182. (Pubitemid 24082591)
33. Komano H, Seeger M, Gandy SE, Wang R, Krafft GA, Fuller RS (1998) Involvement of cell surface glycosyl-phosphatidylinositol-linked aspartyl proteases in α-se-cretase-type cleavage and ectodomain solubilization of human Alzheimer β-amyloid precursor protein in yeast. J Biol Chem 273, 31648-31651. (Pubitemid 29177092)
34. Ledesma MD, Da Silva JS, Crassaerts K, Delacourte A, De Strooper B, Dotti CG (2000) Brain plasmin enhances APP α-cleavage and Aβ degradation and is reduced in Alzhei-mer's disease brains. EMBO Rep 1, 530-535.
35. Chen M, Durr J, Fernandez HL (2000) Possible role of cal-pain in normal processing of β-amyloid precursor protein in human platelets. Biochem Biophys Res Commun 273, 170-175. (Pubitemid 30426881)
36. Chen M, Fernandez HL (2005) μ-calpain is functionally required for α-processing of Alzheimer's β-amyloid precur-sor protein. Biochem Biophys Res Commun 330, 714-721. (Pubitemid 40462146)
37. Black RA, Rauch CT, Kozlosky CJ, Peshon JJ, Slack JL, Wolfson MF, Castner BJ, Stocking KL, Reddy P, Srinivasan S, Nelson N, Boiani N, Schooley KA, Gerhart M, Davis R, Fitzner JN, Johnson RS, Paxton RJ, March CJ, Cerretti DP (1997) A metalloproteinase disintegrin thatreleases tumour-necrosis factor-a from cells. Nature 385, 729-733. (Pubitemid 27098094)
38. Buxbaum JD, Liu KN, Luo Y, Slack JL, Stocking KL, Peschon JJ, Johnson RS, Castner BJ, Cerretti DP, Black RA (1998) Evidence that tumor necrosis factor α-converting enzyme is involved in regulated α-secretase cleavage of the Alzheimer amyloid protein precursor. J Biol Chem 273, 27765-27767. (Pubitemid 28496060)
39. Slack BE, Ma LK, Seah CC (2001) Constitutive shedding of the amyloid precursor protein ectodomain is up-regu-lated by tumour necrosis factor-a converting enzyme. Biochem J 357, 787-794. (Pubitemid 32735158)
40. Asai M, Hattori C, Szabo B, Sasagawa N, Maruyama K, Tanuma SI, Ishiura S (2003) Putative function of ADAM9, ADAM10, and ADAM17 as APPα-secretase. Biochem Bio-phys Res Commun 301, 231-235. (Pubitemid 36268873)
41. Allinson TMJ, Parkin ET, Condon TP, Schwager SLU, Sturrock ED, Turner AJ, Hooper NM (2004) The role of ADAM10 and ADAM17 in the ectodomain shedding of angiotensin converting enzyme and the amyloid precursor protein. Eur J Biochem 271, 2539-2547. (Pubitemid 38813584)
42. Blacker M, Noe MC, Carty TJ, Goodyer CG, LeBlanc AC (2002) Effect of tumor necrosis factor-a converting enzyme (TACE) and metalloprotease inhibitor on amyloid precur-sor protein metabolism in human neurons. J Neurochem 83, 1349-1357. (Pubitemid 35477474)
43. Skovronsky DM, Fath S, Lee VM, Milla ME (2001) Neu-ronal localization of the TNFa converting enzyme (TACE) in brain tissue and its correlation to amyloid plaques. J Neurobiol 49, 40-46.
44. Kim ML, Zhang B, Mills IP, Milla ME, Brunden KR, Lee VMY (2008) Effects of TNFα-converting enzyme inhibition on amyloid β production and APP processing in vitro and in vivo. J Neurosci 28, 12052-12061.
45. Lammich S, Kojro E, Postina R, Gilbert S, Pfeiffer R, Jasionowski M, Haass C, Fahrenholz F (1999) Constitutive and regulated α-secretase cleavage of Alzheimer's amyloid precursor protein by a disintegrin metalloprotease. Proc Natl Acad Sci USA 96, 3922-3927. (Pubitemid 29169012)
46. Lopez-Perez E, Zhang Y, Frank SLJ, Creemers J, Seidah N, Checler F (2001) Constitutive α-secretase cleavage of the β-amyloid precursor protein in the furin-deficient LoVo cell line: involvement of the pro-hormone convertase 7 and the disintegrin ADAM10. J Neurochem 76, 1532-1539. (Pubitemid 32198257)
47. Hartmann D, De Strooper B, Serneels L, Craesserts K, Herreman A, Annaert W, Umans L, Lübke T, Illert AL, von Figura K, Saftig P (2002) The disintegrin/metalloprotease ADAM10 is essential for notch signalling but not for-secretase activity in fibroblasts. Hum Mol Genet 11, 2615-2624.
48. Kuhn PH, Wang H, Dislich B, Colombo A, Zeitschel U, Ellwart JW, Kremmer E, Robner S, Lichtenthaler SF (2010) ADAM10 is the physiologically relevant, constitutive-secretase of the amyloid precursor protein in primary neurons. EMBO J 29, 3020-3032.
49. Postina R, Schroeder A, Dewachter I, Bohl J, Schmitt U, Kojro E, Prinzen C, Endres K, Hiemke C, Blessing M, Flamez P, Dequenne A, Godaux E, van Leuven F, Fahrenholz F (2004) A disintegrin-metalloproteinase prevents amyloid plaque formation and hippocampal defects in an Alzheimer disease mouse model. J Clin Invest 113, 1456-1464. (Pubitemid 39071701)
50. Kim M, Suh J, Romano D, Truong MH, Mullin K, Hooli B, Norton D, Tesco G, Elliott K, Wagner SL, Moir RD, Becker KD, Tanzi RE (2009) Potential late-onset Alzheimer's diseaseassociated mutations in the ADAM10 gene attenuate-secretase activity. Hum Mol Genet 18, 3987-3996.
51. Koike H, Tomioka S, Sorimachi H, Saido TC, Maruyama K, Okuyama A, Fujisawa-Sehara A, Ohno S, Suzuki K, Ishiura S (1999) Membrane-anchored metalloprotease MDC9 has an-secretase activity responsible for processing the amyloid precursor protein. Biochem J 343, 371-375.
52. Hotoda N, Koike H, Sasagawa N, Ishiura S (2002)Asecreted form of human ADAM9 has an-secretase activity for APP. Biochem Biophys Res Commun 293, 800-805.
53. Alfa Cisśe M, Sunyach C, Lefranc-Jullien S, Postina R, Vincent B, Checler F (2005) The disintegrin ADAM9 indirectly contributes to the physiological processing of cellular prion by modulating ADAM10 activity. J Biol Chem 280, 40624-40631. (Pubitemid 41780553)
54. Parkin E, Harris B (2009) A disintegrin and metalloproteinase (ADAM)-mediated ectodomain shedding of ADAM10. J Neurochem 108, 1464-1479.
55. Tousseyn T, Thathiah A, Jorissen E, Raemaekers T, Konietzko U, Reiss K, Maes E, Snellinx A, Serneels L, Nyabi O, Annaert W, Saftig P, Hartmann D, De Strooper B (2009) ADAM10, the rate-limiting protease of regulated intramembrane proteolysis of Notch and other protein, is processed by ADAMS-9, ADAMS-15, and the-secretase. J Biol Chem 284, 11738-11747.
56. Tanabe C, Hotoda N, Sasagawa N, Sehara-Fujisawa A, Maruyama K, Ishiura S (2007) ADAM19 is tightly associated with constitutive Alzheimer's disease APP-secretase in A172 cells. Biochem Biophys Res Commun 352, 111-117. (Pubitemid 44821101)
57. Talamagas AA, Efthimiopoulos S, Tsilibary EC, Figueiredo-Pereira ME, Tzinia AK (2007) Abeta (1-40)-induced secretion of matrix metalloproteinase-9 results in sAPP- release by association with cell surface APP. Neurobiol Dis 28, 304-315.
58. Buxbaum JD, Koo EH, Greengard P (1993) Protein phosphorylation inhibits production of Alzheimer amyloid beta/A4 peptide. Proc Natl Acad Sci USA 90, 9195-9198. (Pubitemid 23306479)
59. Gabuzda D, Busciglio J, Yankner BA (1993) Inhibition of-amyloid production by activation of protein kinase C. J Neurochem 61, 2326-2329.
60. Hung AY, Haass C, Nitsch RM, Qiu WQ, Citron M, Wurtman RJ, Growdon JH, Slekoe DJ (1993) Activation of protein kinase C inhibits cellular production of the amyloid-protein. J Biol Chem 268, 22959-22962. (Pubitemid 23327996)
61. Jacobsen JS, Spruyt MA, Brown AM, Sahasrabudhe SR, Blume AJ, Vitek MP, Muenkel HA, Sonnenberg-Reines J (1994) The release of Alzheimer's disease-amyloid peptide is reduced by phorbol treatment. J Biol Chem 269, 8376-8382.
62. LeBlanc AC, Koutroumanis M, Goodyer CG (1998) Protein kinase C activation increases release of secreted amyloid precursor protein without decreasing A- production in human primary neuron cultures. J Neurosci 18, 2907-2913. (Pubitemid 28163220)
63. Savage M, Trusko SP, Howland DS, Pinsker LR, Mistretta S, Reaume AG, Greenberg BD, Siman R, Scott RW (1998) Turnover of amyloid protein in mouse brain and acute reduction of its level by phorbol ester. J Neurosci 18, 1743-1752. (Pubitemid 28103082)
64. Etcheberrigaray R, Tan M, Dewachter I, Kuiṕeri C, Van der Auwera I, Wera S, Qiao L, Bank B, Nelson TJ, Kozikowski AP, Van Leuven F, Alkon DL (2004) Therapeutic effects of PKC activator in Alzheimer's disease transgenic mice. Proc Natl Acad Sci USA 101, 11141-11146. (Pubitemid 38989597)
65. Caccamo A, Oddo S, Billings LM, Green KN, Martinez-Coria H, Fisher A, LaFerla FM (2006) M1 receptors play a central role in modulating AD-like pathology in transgenic mice. Neuron 49, 671-682. (Pubitemid 43290127)
66. Roner S, Beck M, Stahl T, Mendla K, Schliebs R, Bigl V (2000) Constitutive overactivation of protein kinase C in guinea pig brain increases-secretory APP processing without decreasing-amyloid generation. Eur J Neurosci 12, 3191-3200.
67. Gandhi S, Refolo LM, Sambamurti K (2004) Amyloid precursor protein compartmentalization restricts-amyloid production: therapeutic targets based on BACE compartmentalization. J Mol Neurosci 24, 137-144.
68. Skovronsky DM, Moore DB, Milla ME, Doms RW, Lee VM (2000) Protein kinase C-dependent alpha-secretase competes with beta-secretase for cleavage of amyloid-beta precursor protein in the trans-Golgi network. J Biol Chem 275, 2568-2575. (Pubitemid 30082022)
69. J̈ager S, Leuchtenberger S, Martin A, Czirr E, Wesselowski J, Dieckmann M, Waldron E, Korth C, Koo EH, Heneka M, Weggen S, Pietrzik CU (2009) secretase mediated conversion of the amyloid precursor protein derived membrane stub C99 to C83 limits A- generation. J Neurochem 111, 1369-1382.
70. Portelius E, Price E, Brinkmalm G, Stiteler M, Olsson M, Persson R, Westman-Brinkmalm A, Zetterberg H, Simon AJ, Blennow K (2009) A novel pathway for amyloid precursor protein processing. Neurobiol Aging. doi:10.1016/j. neurobiolaging.2009.06.002
71. Palacino JJ, Berechid BE, Alexander P, Eckman C, Younkin S, Nye JS, Wolozin B (2000) Regulation of amyloid precursor protein processing by presenilin 1 (PS1) and PS2 in PS1 knockout cells. J Biol Chem 275, 215-222. (Pubitemid 30038974)
72. Yankner BA, Dawes LR, Fisher S, Villa-Komaroff L, Oster-Granite ML, Neve RL (1989) Neurotoxicity of a fragment of the amyloid precursor associated with Alzheimer's disease. Science 245, 417-420. (Pubitemid 19203368)
73. Neve RL, Kammesheidt A, Hohmann CF (1992) Brain transplants of cells expressing the carboxy-terminal fragment of the Alzheimer amyloid protein precursor cause specific neuropathology in vivo. Proc Natl Acad Sci USA 89, 3448-3452.
74. Kammesheidt A, Boyce FM, Spanoyannis AF, Cummings BJ, Ortegon M, Cotman C, Vaught JL, Neve RL (1992) Deposition of beta/A4 immunoreactivity and neuronal pathology in transgenic mice expressing the carboxyterminal fragment of the Alzheimer amyloid precursor in the brain. Proc Natl Acad Sci USA 89, 10857-10861.
75. Oster-Granite ML, McPhie DL, Greenan J, Neve RL (1996) Age-dependent neuronal and synaptic degeneration in mice transgenic for the C-terminus of the amyloid precursor protein. J Neurosci 16, 6732-6741. (Pubitemid 26359357)
76. Nalbantoglu J, Tirado-Santiago G, Lahsaini A, Poirier J, Goncalves O, Verge G, Momoli F, Welner SA, Massicotte G, Julien JP, Shapiro ML (1997) Impaired learning and LTP in mice expressing the carboxy terminus of the Alzheimer amyloid precursor protein. Nature 387, 500-505. (Pubitemid 27235467)
77. Lalonde R, Dumont Fukuchi K, Strazielle C (2002) Trangenic mice expressing the human C99 terminal frag-ment of βAPP: effects on spatial learning, exploration, anxiety, and motor coordination. Exp Gerontol 37, 1399-1410. (Pubitemid 36143762)
78. Passer B, Pellegrini L, Russo C, Siegel RM, Lenardo MJ, Schettini G, Bachmann M, Tabaton M, D'Adamio L (2000) Generation of an apoptotic intracellular peptide by gamma-secretase cleavage of Alzheimer's amyloid beta protein precursor. J Alzheimers Dis 2, 289-301. (Pubitemid 32095613)
79. Chang KA, Suh YH (2010) Possible roles of amyloid intra-cellular domain of amyloid precursor protein. BMB Rep 43, 656-663.
80. Cao X, Südhof TC (2001) A transcriptionally active com-plex of APP with Fe65 and histone acetyltransferase Tip60. Science 293, 115-120. (Pubitemid 32625507)
81. Kimberly WT, Zheng JB, Guenette SY, Selkoe DJ (2001) The intracellular domain of beta-amyloid precursor protein is stabilized by Fe65 and translocates to the nucleus in a notch-like manner. J Biol Chem 276, 40288-40292.
82. Kim HS, Kim EM, Lee JP, Park CH, Kim S, Seo JH, Chang KA, Yu E, Jeong SJ, Suh YH (2003) C-terminal fragments of amyloid precursor protein exert neurotoxicity by inducing glycogen synthase kinase-3 beta expression. FASEB J 17, 1951-1953.
83. von Rotz RC, Kohli BM, Bosset J, Meier M, Suzuki T, Nitsch RM, Konietzko U (2004) The APP intracellular domain forms nuclear multiprotein complewes and regulates the transcription of its own precursor. J Cell Sci 117, 4435-4448. (Pubitemid 39360070)
84. Pardossi-Piquard R, Petit A, Kawarai T, Sunyach C, Alves da Costa C, Vincent B, Ring S, D'Adamio L, Shen J, Müller U, St Georges-Hyslop P, Checler F (2005) Presenilin-dependent transcriptional control of the Aβ-degrading enzyme neprilysin by intracellular domains of βAPP and APLP Neuron 46, 541-554. (Pubitemid 40797380)
85. Alves da Costa C, Sunyach C, Pardossi-Piquard R, Sévalle J, Vincent B, Boyer N, Kawarai T, Girardot N, St Georges-Hyslop P, Checler F (2006) Presenilin-dependent "y-se-cretase-mediated control of p53-associated cell death in Alzheimer's disease. JNeurosci 26, 6377-6385.
86. Ryan KA, Pimplikar SW (2005) Activation of GSK-3 and phosphorylation of CRMP2 in transgenic mice expressing APP intracellular domain. J Cell Biol 171, 327-335. (Pubitemid 41540024)
87. Goodger ZV, Rajendran L, Trutzel A, Kohli BM, Nitsch RM, Konietzko U (2009) Nuclear signaling by the APP intracellular domain occurs predominantly through the amy-loidogenic pathway. J Cell Sci 122, 3703-3714.
88. Mattson MP, Cheng B, Culwell AR, Esch FS, Lieberburg I, Rydel RE (1993) Evidence for excitoprotective and intra-neuronal calcium-regulating roles for secreted forms of the β-amyloid precursor protein. Neuron 10, 243-254. (Pubitemid 23079546)
89. + channels and suppression of neuronal activity by secreted β-amyloid precursor protein. Nature 379, 74-78. (Pubitemid 26008138)
90. Furukawa K, Mattson MP (1998) Secreted amyloid precur-sor protein a selectively suppresses N-methyl-D-aspartate currents in hippocampal neurons: involvement of cyclic AMP Neuroscience 83, 429-438. (Pubitemid 28062633)
91. Copanaki E, Chang S, Vlachos A, Tschäpe JA, Müller UC, Kögel D, Deller T (2010) sAPPa antogonizes dendritic degeneration and neuron death tfiggered by proteasomal stress. Mol Cell Neurosci 44, 386-393.
92. Moechars D, Lorent K, De Stroopper B, Dewachter I, Van Leuven F (1996) Expression in brain of amyloid precur-sor protein mutated in the α-secretase site causes disturbed behavior, neuronal degeneration and premature death in transgenic mice. EMBO J15, 1265-1274. (Pubitemid 26093462)
93. Meziane H, Dodart JC, Mathis C, Little S, Clemens J, Paul SM, Ungerer A (1998) Memory-enhancing effects of secreted forms of the beta-amyloid precursor protein in nor-mal and amnestic mice. Proc Natl Acad Sci USA 95, 12683-12688. (Pubitemid 28483825)
94. Ring S, Weyer SW, Kilian SB, Waldron E, Pietrzik CU, Filippov MA, Herms J, Buchholz C, Eckman CB, Korte M, Wolfer DP, Müller UC (2007) The secreted beta-amyloid precursor protein ectodomain APPs alpha is sufficient to rescue the anatomical, behavioral, and electrophysiological abnormalities of APP-deficient mice. J Neurosci 27, 7817-7826. (Pubitemid 47093823)
95. Saitoh T, Sundsmo M, Roch JM, Kimura N, Cole G, Schubert D, Oltersdorf T, Schenk DB (1989) Secreted form of amyloid β protein precursor is involved in the growth regulation of fibroblasts. Cell 58, 615-622. (Pubitemid 19210955)
96. Jin LW, Ninomiya H, Roch JM, Schubert D, Masliah E, Otero DAC, Saitoh T (1994) Peptides containing the RERMS sequence of amyloid β/A4 protein precursor bind cell surface and promote neurite extension. J Neurosci 14, 5461-5470. (Pubitemid 24279065)
97. Quast T, Wehner S, Kirfel G, Jaeger K, De Luca M, Herzog V (2003) sAPP as a regulator of dendritic motility and melanin release in epidermal melanocytes and melanoma cells. FASEB J17, 1739-1741.
98. Hansel DE, Rahman A, Wehner S, Herzog V, Yeo CJ, Maitra A (2003) Increased expression and processing of the Alzheimer amyloid precursor protein in pancreatic cancer may influence proliferation. Cancer Res 63, 7032-7037. (Pubitemid 37413434)
99. Furukawa K, Sopher BL, Rydel RE, Begley JG, Pham DG, Martin GM, Fox M, Mattson MP (1996) Increased activity-regulating and neuroprotective efficacy of α-secretase-derived secreted amyloid precursor protein conferred by a C-terminal heparin-binding domain. J Neu-rochem 67, 1882-1896. (Pubitemid 26349661)
100. Gralle M, Gralle Botelho M, Wouters FS (2009) Neuropro-tective secreted amyloid precursor protein acts by disrupting amyloid precursor protein dimers. J Biol Chem 284, 15016-15025.
101. Prinzen C, Müller U, Endres K, Fahrenholz F, Postina R (2005) Genomic structure and functional characterization ofthehumanADAM10promoter. FASEB J19, 1522-1524. (Pubitemid 41279018)
102. Mizui Y, Yamazaki K, Sagane K, Tanaka I (1999) cDNA cloning of mouse tumor necrosis factor-a-converting enzyme (TACE) and partial analysis of its promoter. Gene 233, 67-74. (Pubitemid 29353225)
103. Cerretti DP, Poindexter K, Castner BJ, Means G, Copeland NG, Gilbert DJ, Jenkins NA, Black RA, Nelson N (1999) Characterization of the cDNA and gene for mouse tumour necrosis factor a converting enzyme (TACE/ADAM17) and its location to mouse chromosome 12 and human chromo-some 2p25. Cytokines 11, 541-551. (Pubitemid 29368971)
104. Tippmann F, Hundt J, Schneider A, Endres K, Fahrenholz F (2009) Up-regulation of the α-secretase ADAM10 by retinoic acid receptors and acitretin. FASEB J 23, 1643-1654.
105. Donmez G, Wang D, Cohen DE, Guarente L (2010) SIRT1 suppresses β-amyloid production by activating the α-secretase gene ADAM10. Cell 142, 320-332.
106. Tachida Y, Nakagawa K, Saito T, Saido TC, Honda T, Saito Y, Murayama S, Endo T, Sakaguchi G, Kato A, Kitazume S, Hashimoto Y (2008) Interleukin-1 β up-regulates TACE to enhance α-cleavage of APP in neurons: resulting decrease in Aβ production. JNeurochem 104, 1387-1393. (Pubitemid 351293352)
107. Fieber C, Baumann P, Vallon R, Termeer C, Simon JC, Hofmann M, Angel P, Herrlich P, Sleeman JP (2004) Hyaluronan-oligosaccharide-induced transcription of met-alloproteases. J Cell Sci 117, 359-367.
108. Marcello E, Gardoni F, Mauceri D, Romorini S, Jeromin A, Epis R, Borroni B, Cattabeni F, Sala C, Padovani A, Di Luca M (2007) Synapse-associated protein-97 mediates α-secretase ADAM10 trafficking and promotes its activity. JNeurosci 27, 1682-1691. (Pubitemid 46280085)
109. Peiretti F, Deprez-Beauclair P, Bonardo B, Aubert H, Juhan-Vague I, Nalbone G (2003) Identification of SAP97 as an intracellular binding partner of TACE. J Cell Sci116, 1949-1957. (Pubitemid 36622293)
110. Tanaka M, Nanba D, Mori S, Shiba F, Ishiguro H, Yoshino K, Matsuura N, Higashiyama S (2004) ADAM binding pro-tein eve-1 is required for ectodomain shedding of epidermal growth factor receptor ligands. J Biol Chem 279, 41950-41959. (Pubitemid 39313645)
111. Poghosyan Z, Robbins SM, Houslay MD, Webster A, Murphy G, Edwards DR (2002) Phosphorylation-dependent interactions between ADAM15 cytoplasmic domain and src family protein-tyrosine kinases. J Biol Chem 277, 4999-5007. (Pubitemid 34968539)
112. Mori S, Tanaka M, Nanba D, Nishiwaki E, Ishiguro H, Higashiyama S, Matsuura N (2003) PACSIN3 binds ADAM12/meltrin α and up-regulates ectodomain shedding of heparin-binding epidermal growth factor-like growth fac-tor. J Biol Chem 278, 46029-46034. (Pubitemid 37432752)
113. Canault M, Tellier E, Bonardo B, Mas E, Aumailley M, Juhan-Vague I, Nalbone G, Peiretti F (2006) FHL2 inter-acts with both ADAM-17 and the cytoskeleton and regulates ADAM-17 localization and activity. J Cell Physiol 208, 363-372. (Pubitemid 43993427)
114. Tang MX, Jacobs D, Stern Y, Marder K, Schofield P, Gurland B, Andrews H, Mayeux R (1996) Effect of oestrogen during menopause on risk and age at onset of Alzheimer's disease. Lancet 348, 429-432. (Pubitemid 26267873)
115. Swerdloff RS, Wang C (1993) Androgens and aging men. Exp Gerontol 28, 435-446.
116. Xu H, Gouras GK, Greenfield JP, Vincent B, Naslund J, Mazzarelli L, Fried G, Jovanovic JN, Seeger M, Relkin NR, Liao F, Checler F, Buxbaum JD, Chait BT, Thinakaran G, Sisodia SS, Wang R, Greengard P, Gandy S (1998) Estro-gen reduces neuronal generation of Alzheimer β-amyloid peptides. Nature Med 4, 447-451. (Pubitemid 28212761)
117. Gouras GK, Xu H, Gross RS, Greenfield JP, Hai B, Wang R, Greengard P (2000) Testosterone reduces neuronal secre-tion of Alzheimer's β-amyloid peptides. Proc Natl Acad Sci US A97, 1202-1205. (Pubitemid 30080836)
118. Greenfield JP, Leung LW, Cai D, Kaasik K, Gross RS, Rodriguez-Boulan E, Greengard P, Xu H (2002) Estro-gen lowers Alzheimer β-amyloid generation by stimulating trans-Golgi network vesicle biogenesis. J Biol Chem 277, 12128-12136. (Pubitemid 34952777)
119. Epis R, Marcello E, Gardoni F, Longhi A, Calvani M, Iannucelli M, Cattabeni F, Canonico PL, Di Luca M (2008) Modulatory effect of acetyl-L-carnitine on amyloid precursor protein metabolism in hippocampal neurons. Eur J Pharmacol 597, 51-56.
120. Yang HQ, Sun ZK, Ba MW, Xu J, Xing Y (2009) Involve-ment of protein trafficking in deprenyl-induced α-secretase activity regulation in PC12 cells. Eur J Pharmacol 610, 37-41.
121. Hou Y, Yu YB, Liu G, Luo Y (2009) A natural squa-mosamide derivative FLZ reduces amyloid-β produc-tion by increasing non-amyloidogenic βAPP processing. J Alzeimers Dis 18, 153-165.
122. Bodovitz S, Klein WL (1996) Cholesterol modulates α-secretase cleavage of amyloid precursor protein. J Biol Chem 271, 4436-4440.
123. Howland DS, Trusko SP, Savage MJ, Reaume AG, Lang DM, Hirsch JD, Maeda N, Siman R, Greenberg BD, Scott RW, Flood DG (1998) Modulation of secreted β-amyloid precursor protein and amyloid β-peptide in brain by choles-terol. J Biol Chem 273, 16576-16582.
124. Galbete JL, Rodriguez-Martin T, Peressini E, Modena P, Bianchi R, Forloni G (2000) Cholesterol decreases secretion of the secreted form of amyloid precursor protein by inter-fering with glycosylation in the protein secretory pathway. Biochem J 348, 307-313. (Pubitemid 30345202)
125. Kojro E, Gimpl G, Lammich S, Marz W, Fahrenholz F (2001) Low cholesterol stimulates the nonamyloidogenic pathway by its effect on the α-secretase ADAM10. Proc Natl Acad Sci USA 98, 5815-5820. (Pubitemid 32435725)
126. Yan Y, Shirakabe K, Werb Z (2002) The metalloprorease Kuzbanian (ADAM10) mediates the transactivation of EGF receptor by G-protein-coupled receptors. J Cell Biol 158, 221-226.
127. Xu D, Sharma C, Hemler ME (2009) Tetraspanin12 reg-ulates ADAM10-dependent cleavage of amyloid precursor protein. FASEB J 23, 3674-3681.
128. Tanabe C, Ebina M, Asai M, Futai E, Sasagawa N, Katano K, Fukami H, Ishiura S (2009) 1, 3-capryloyl-2-arachidonoyl glycerol activates α-secretase activity and suppresses Aβ40 secretion in A172 cells. Neurosci Lett 450, 324-326.
129. Zhang Y, Zhang H, Hua S, Ma L, Chen C, Liu X, Jiang L, Yang H, Zhang P, Yu D, Guo Y, Tan X, Liu J (2007) Iden-tification of two herbal compounds with potential choles-terol-lowering activity. Biochem Pharmacol 74, 940-947. (Pubitemid 47212078)
130. Colciaghi F, Borroni B, Zimmermann M, Bellone C, Longhi A, Padovani A, Cattabeni F, Christen Y, Di Luca M (2004) Amyloid precursor protein metabolism is regulated toward alpha-secretase pathway by Ginkgo biloba extracts. Neuro-biolDis 16, 454-460. (Pubitemid 38757325)
131. Walev I, Vollmer P, Palmer M, Bhakdi S, Rose-John S (1996) Pore-forming toxins trigger shedding of receptors for inter-leukin 6 and lipopolysaccaride. Proc Natl Acad Sci USA 93, 7882-7887. (Pubitemid 26277133)
132. Mei Z, Zhang F, Tao L, Zheng W, Cao Y, Wang Z, Trang S, Le K, Chen S, Pi R, Liu P (2009) Cryptotanshinone, a compound from Salvia miltiorrhiza modulates amyloid precursor protein metabolism and attenuates β-amyloid deposition
133. Mei Z, Situ B, Tan X, Zheng S, Zhang F, Yan P, Liu P (2010) Cryptotanshinone upregulates alpha-secretase by activation of PI3 K pathway in cortical neurons. Brain Res 1348, 165-173.
134. Edwards DR, Handsley MM, Pennington CJ (2008) The ADAM metalloproteases. Mol Asp Med 29, 258-289.
135. Galazka G, Windsor LJ, Birkedal-Hansen H, Engler JA (1996) APMA (4-aminophenylmercuric acetate) activation of stromelysin-1 involves protein interactions in addition to those with cysteine-75 in the propeptide. Biochemistry 35, 11221-11227. (Pubitemid 26298758)
136. Sanderson MP, Erickson SN, Gough PJ, Garton KJ, Wille PT, Raines EW, Dunbar AJ, Dempsey PJ (2005) ADAM10 mediates ectodomain shedding of the betacellulin precursor activated by p-aminophenylmercuric acetate and extracellular calcium influx. J Biol Chem 280, 1826-1837.
137. Levites Y, Amit T, Mandel S, Youdim MB (2003) Neuroprotection and neurorescue against Abeta toxicity and PKC-dependent release of nonamyloidogenic soluble precursor protein by green tea polyphenol (-)-epigallocatechin-3- gallate. FASEB J 17, 952-954.
138. Obregon DF, Rezai-Zadeh K, Bai Y, Sun N, Hou H, Ehrhart J, Zeng J, Mori T, Arendash GW, Shytle D, Town T, Tan J (2006) ADAM10 activation is required for green tea (-)-epigallocatechin-3-gallate-induced-secretase cleavage of amyloid precursor protein. J Biol Chem 281, 16419-16427.
139. Willems SH, Tape CJ, Stanley PL, Taylor NA, Mills IG, Neal DE, McCafferty J, Murphy G (2010) Thiol isomerases negatively regulate the cellular shedding activity of ADAM17. Biochem J 428, 439-450.
140. Alkon DL, Sun MK, Nelson TJ (2007) PKC signaling deficits: a mechanistic hypothesis for the origins of Alzheimer's disease. Trends in Pharmacol Sci 28, 51-60. (Pubitemid 46161834)
141. Diaz-Rodriguez E, Montero JC, Esparis-Ogando A, Yuste L, Pandiella A (2002) Extracellular signal-regulated kinase phosphorylates tumor necrosis factor-converting enzyme at threonine 735: a potential role in regulated shedding. Mol Biol Cell 13, 2031-2044.
142. Zheng Y, Schlondorff J, Blobel CP (2002) Evidence for regulation of the tumor necrosis factor alpha-convertase (TACE) by protein-tyrosine phosphatase PTPH1. J Biol Chem 277, 42463-42470. (Pubitemid 35285612)
143. Zhang Q, Thomas SM, Wai Yan Lui V, Xi S, Siegfried JM, Fan H, Smithgall TE, Mills GB, Grandis JR (2006) Phosphorylation of TNF- converting enzyme by gastrin-releasing peptide induces amphiregulin release and EGF receptor activation. Proc Natl Acad Sci USA 103, 6901-6906.
144. Kozikowski AP, Nowak I, Petukhov PA, Etcheberrigaray R, Mohamed A, Tan M, Lewin N, Hennings H, Pearce LL, Blumberg PM(2003) Newamide-bearing benzolactambased protein kinase C modulators induce enhanced secretion of the amyloid precursor protein metabolite sAPP. J Med Chem 46, 364-373. (Pubitemid 36139789)
145. Suzuki T, Oishi M, Marshak DR, Czernik AJ, Nairn AC, Greengard P (1994) Cell cycle-dependent regulation of the phosphorylation and metabolism of the Alzheimer amyloid precursor protein. EMBO J 13, 1114-1122. (Pubitemid 24074718)
146. Xu H, Sweeney D, Greengard P, Gandy SE (1996) Metabolism of Alzheimer-amyloid precursor protein: regulation by protein kinase A in intact cells and in a cell-free system. Proc Natl Acad Sci USA 93, 4081-4084.
147. Petanceska SS, Gandy SE (1999) The phosphatidylinositol 3-kinase inhibitor wortmannin alters the metabolism of the Alzheimer's amyloid precursor protein. J Neurochem 73, 2316-2320.
148. Ro-ner S, Ueberham U, Schliebs R, Perez-Polo JR, Bigl V (1999) Regulated secretion of amyloid precursor protein by TrkA receptor stimulation in rat pheochromocytoma-12 cells is mitogen activated protein kinase sensitive. Neurosci Lett 271, 97-100. (Pubitemid 29400676)
149. Mudher A, Chapman S, Richardson J, Asuni A, Gibb G, Pollard C, Killick R, Iqbal T, Raymond L, Varndell I, Sheppard P, Makoff A, Gower E, Siden PE, Lewis P, Murphy M, Golde TE, Rupniak HT, Anderton BH, Lovestone S (2001) Dishevelled regulates the metabolism of amyloid precursor protein via protein kinase C/mitogen-activated protein kinase and c-jun terminal kinase. J Neurosci 21, 4987-4995. (Pubitemid 32622924)
150. Phiel CJ, Wilson CA, Lee VMY, Klein PS (2003) GSK-3- regulates production of Alzheimer's disease amyloid- peptides. Nature 423, 435-439.
151. Maillet M, Robert SJ, Cacquevel M, Gastineau M, Vivien D, Bertoglio J, Zugaza JL, Fischmeister R, Lezoualc'h F (2003) Crosstalk between Rap1 and Rac regulates secretion of sAPP-. Nature Cell Biol 5, 633-639. (Pubitemid 36818085)
152. Liu F, Su Y, Li B, Ni B (2003) Regulation of amyloid precursor protein expression and secretion via activation of ERK1/2 by hepatocyte growth factor in HEK293 cells transfected with APP751. Exp Cell Res 287, 387-396. (Pubitemid 37323850)
153. Pedrini S, Carter TL, Prendergast G, Petanceska S, Ehrlich ME, Gandy S (2005) Modulation of statin-activated shedding of Alzheimer APP ectodomain by ROCK. Plos Medicine 2, 69-78.
154. Bandyopadhyay S, Hartley DM, Cahill CM, Lahiri DK, Chattopadhyay N, Rogers JT (2006) Interleukin-1- stimulates non-amyloidogenic pathway by-secretase (ADAM-10 and ADAM-17) cleavage of APP in human astrocytic cells involving p38 MAP kinase. J Neurosci Res 84, 106-118.
155. Gianni D, Zambrano N, Bimonte M, Minopoli G, Mercken L, Talamo F, Scaloni A, Russo T (2003) Platelet-derived growth factor induces the-secretase-mediated cleavage of Alzheimer's amyloid precursor protein through a Src-Rac-dependent pathway. J Biol Chem 278, 9290-9297.
156. Refolo LM, Salton SRJ, Anderson JP, Mehta P, Robakis NK (1989) Nerve and epidermal growth factors induce the release of the Alzheimer amyloid precurssor protein from PC12 cell cultures. Biochem Biophys Res Commun 164, 664-670. (Pubitemid 19280320)
157. Nitsch RM, Slack BE, Wurtman RJ, Growdon JH (1992) Release of Alzheimer amyloid precursor derivatives stimulated by activation of muscarinic acetylcholine receptors. Science 258, 304-307.
158. Davis-Salinas J, Saporito-Irwin SM, Donovan FM, Cunningham DD, Van Nostrand WE (1994) Thrombin receptor activation induces secretion and nonamyloidogenic processing of amyloid-protein precursor. J Biol Chem 269, 22623-22627. (Pubitemid 24273369)
159. Lee RKK, Wurtman RJ, Cox AJ, Nitsch RM (1995) Amyloid precursor protein processing is stimulated by metabotropic glutamate receptors. Proc Natl Acad Sci USA 92, 8083-8087.
160. Nitsch RM, Kim C, Growdon JH (1998) Vasopressin and bradykinin regulate secretory processing of the amyloid protein precursor of Alzheimer's disease. Neurochem Res 23, 807-814. (Pubitemid 28173588)
161. Kojro E, Postina R, Buro C, Meiringer C, Gehrig-Burger K, Fahrenholz F (2006) The neuropeptide PACAPpromotes the-secretase pathway for processing the Alzheimer amyloid precursor protein. FASEB J 20, 512-514.
162. Vincent B, Alfa Cisśe M, Sunyach C, Guillot-Sestier MV, Checler F (2008) Regulation of-APP and PrPc cleavage by-secretase: mechanistic and therapeutic perspectives. Curr Alz Res 5, 202-211.
163. Soond S, Everson B, Riches DWH, Murphy G (2005) ERKmediated phosphorylation of Thr735 in TNF-converting enzyme and its potential role in TACE protein trafficking. J Cell Sci 118, 2371-2380.
164. Fisher A, Brandeis R, Bar-Ner RHN, Kliger-Spatz M, Natan N, Sonego H, Marcovitch I, Pittel Z (2002) AF150(S) and AF267B. M1 Muscarinic agonists as innovative therapies for Alzheimer's disease. J Mol Neurosci 19, 145-153. (Pubitemid 35013348)
165. Pike CJ, Overman MJ, Cotman CW (1995) Amino-terminal deletions enhance aggregation of β-amyloid peptides in vitro. J Biol Chem 270, 23895-23898.
166. Szczepanik AM, Rampe D, Ringheim GE (2001) Amy-loid-β peptide fragments p3 and p4 induce pro-inflammatory cytokine and chemokine production in vitro and in vivo. J Neurochem 77, 304-317. (Pubitemid 32245104)
167. Wei W, Norton DD, Wang X, Kusiak JW (2002) Abeta 17-42 in Alzheimer's disease activates JNK and caspase-8leading to neuronal apoptosis. Brain 125, 2036-2043.
168. Jang H, Teran Arce F, Ramachandran S, Capone R, Azimova R, Kagan BL, Nussinov R, Lal R (2010) Truncated β-amyloid peptide channels provide an alternative mechanism for Alzheimer's disease and Down syndrom. Proc Natl Acad Sci USA 107, 6538-6543.
169. Vincent B, Checler F (2011) α-secretase in Alzheimer's dis-ease and beyond: mechanistic, regulation and function in the shedding of membrane proteins. Curr Alz Res (in press).
170. Moore RJ, Owens DM, Stamp G, Arnott C, Burke F, East N, Holdsworth H, Turner L, Rollins B, Pasparakis M, Kollias G, Balkwill F (1999) Mice deficient in tumor necrosis factor-a are resistant to skin carcinogenesis. Nat Med 5, 828-831. (Pubitemid 29318619)
171. Emi M, Katagiri T, Harada Y, Saito H, Inazawa J, Ito I, Kasumi F, Nakamura Y (1993) A novel metalloprotease/disintegrin-like gene at 17q21.3 is somatically rearranged in two primary breast cancers. Nat Genet 5, 151-157. (Pubitemid 23293450)
172. Ko SY, Lin SC, Wong YK, Liu CJ, Chang KW, Liu TY (2007) Increase of disintegrin metalloprotease 10 (ADAM10) expression in oral squamous cell carcinoma. Cancer Lett 245, 33-43.
173. Santiago-Josefat B, Esselens C, Bech-Serra JJ, Arribas J (2007) Post-transcriptional up-regulation of ADAM17 upon epidermal growth factor receptor activation and in breast tumors. J Biol Chem 282, 8325-8331. (Pubitemid 47093613)
174. Szalad A, Katakowski M, Zheng X, Jiang F, Chopp M (2009) Transcription factor Sp1 induces ADAM17 and contributes to tumor cell invasiveness under hypoxia. J Exp Clin Cancer Res 28, 129.
175. Chubinskaya S, Mikhail R, Deutsch A, Tindal MH (2001) ADAM10 protein is present in human articular cartilage primarily in the membrane-bound form and is upregulated in osteoarthritis and in response to IL-1a in bovine nasal cartilage. J Histochem Cytochem 49, 1165-1176. (Pubitemid 32800537)
176. Holdt LM, Thiery J, Breslow JL, Teupser D (2008) Increased ADAM17 mRNA expression and activity is associated with atherosclerosis resistance in LDL-recptor deficient mice. Arterioscler Thromb Vasc Biol 28, 1097-1103.
177. Lathia JD, Mattson MP, Cheng A (2008) Notch: from neu-ronal development to neurological disorders. J Neurochem 107, 1471-1481.
178. He G, Luo W, Li P, Remmers C, Netzer WJ, Hendrick J, Bettayeb K, Flajolet M, Gorelick F, Wennogle LP, Green-gard P (2010) Gamma-secretase activating protein is a ther-apeutic target for Alzheimer's disease. Nature 467, 95-98.