[1]
|
J. Hardy and D. J. Selkoe, “The Amyloid Hypothesis of Alzheimer’s Disease: Progress and Problems on the Road to Therapeutics,” Science, Vol. 297, No. 5580, 2002, pp. 353-356. doi:10.1126/science.1072994
|
[2]
|
E. Karran, M. Mercken and B. D. Strooper, “The Amyloid Cascade Hypothesis for Alzheimer’s Disease: An Appraisal for the Development of Therapeutics,” Nature Reviews Drug Discovery, Vol. 10, No. 9, 2011, pp. 698-712. doi:10.1038/nrd3505
|
[3]
|
S. F. Lichtenthaler, C. Haass and H. Steiner, “Regulated Intramembrane Proteolysis-Lessons from Amyloid Precursor Protein Processing,” Journal of Neurochemistry, Vol. 117, No. 5, 2011, pp. 779-796. doi:10.1111/j.1471-4159.2011.07248.x
|
[4]
|
T. Iwatsubo, A. Odaka, N. Suzuki, H. Mizusawa, N. Nukina and Y. Ihara, “Visualization of Aβ42(43) and Aβ40 in Senile Plaques with End-Specific Aβ Monoclonals: Evidence That an Initially Deposited Species Is Aβ42(43),” Neuron, Vol. 13, No. 1, 1994, pp. 45-53. doi:10.1016/0896-6273(94)90458-8
|
[5]
|
J. T. Jarrett, E. P. Berger and P. T. Lansbury, Jr., “The Carboxy Terminus of the β Amyloid Protein Is Critical for the Seeding of Amyloid Formation: Implications for the Pathogenesis of Alzheimer’s Disease,” Biochemistry, Vol. 32, No. 18, 1993, pp. 4693-4697. doi:10.1021/bi00069a001
|
[6]
|
D. M. Kovacs, H. J. Fausett, K. J. Page, T. W. Kim, R. D. Moir, D. E. Merriam, R. D. Hollister, O. G. Hallmark, R. Mancini, K. M. Felsenstein, B. T. Hyman, R. E. Tanzi and W. Wasco, “Alzheimer-Associated Presenilins 1 and 2: Neuronal Expression in Brain and Localization to Intracellular Membranes in Mammalian Cells,” Nature Medicine, Vol. 2, No. 2, 1996, pp. 224-229. doi:10.1038/nm0296-224
|
[7]
|
K. Shirotani, D. Edbauer, S. Prokop, C. Haass and H. Steiner, “Identification of distinct Gamma-Secretase Complexes with Different APH-1 Variants,” Journal of Biological Chemistry, Vol. 279, No. 40, 2004, pp. 41340-41345. doi:10.1074/jbc.M405768200
|
[8]
|
L. Serneels, T. Dejaegere, K. Craessaerts, K. Horre, E. Jorissen, T. Tousseyn, S. Hebert, M. Coolen, G. Martens, A. Zwijsen, W. Annaert, D. Hartmann and B. De Strooper, “Differential Contribution of the Three Aph1 Genes to Gamma-Secretase Activity in Vivo,” Proceedings of the National Academy of Sciences of USA, Vol. 102, No. 5, 2005, pp. 1719-1724. doi:10.1073/pnas.0408901102
|
[9]
|
S. Arawaka, H. Hasegawa, A. Tandon, C. Janus, F. Chen, G. Yu, K. Kikuchi, S. Koyama, T. Kato, P. E. Fraser and P. St George-Hyslop, “The Levels of Mature Glycosylated Nicastrin Are Regulated and Correlate with Gamma-Secretase Processing of Amyloid β-Precursor Protein,” Journal of Neurochemistry, Vol. 83, No. 5, 2002, pp. 1065-1071. doi:10.1046/j.1471-4159.2002.01207.x
|
[10]
|
F. Chen, A. Tandon, N. Sanjo, Y. J. Gu, H. Hasegawa, S.Arawaka, F. J. Lee, X. Ruan, P. Mastrangelo, S. Erdebil, L. Wang, D. Westaway, H. T. Mount, B. Yankner, P. E. Fraser and P. St George-Hyslop, “Presenilin 1 and Presenilin 2 Have Differential Effects on the Stability and Maturation of Nicastrin in Mammalian Brain,” Journal of Biological Chemistry, Vol. 278, No. 22, 2003, pp. 19974-19979. doi:10.1074/jbc.M210049200
|
[11]
|
K. Ahn, C. C. Shelton, Y. Tian, X. Zhang, M. L. Gilchrist, S. S. Sisodia and Y. M. Li, “Activation and Intrinsic Gamma-Secretase Activity of Presenilin 1,” Proceedings of the National Academy of Sciences of USA, Vol. 107, No. 50, 2010, pp. 21435-21440. doi:10.1073/pnas.1013246107
|
[12]
|
N. Takasugi, T. Tomita, I. Hayashi, M. Tsuruoka, M. Niimura, Y. Takahashi, G. Thinakaran and T. Iwatsubo, “The Role of Presenilin Cofactors in the Gamma-Secretase Complex,” Nature, Vol. 422, No. 6930, 2003, pp. 438-441. doi:10.1038/nature01506
|
[13]
|
Y. W. Zhang, W. J. Luo, H. Wang, P. Lin, K. S. Vetrivel, F. Liao, F. Li, P. C. Wong, M. G. Farquhar, G. Thinakaran and H. Xu, “Nicastrin is Critical for Stability and Trafficking But Not Association of Other Presenilin/ Gamma-Secretase Components,” Journal of Biological Chemistry, Vol. 280, No. 17, 2005, pp. 17020-17026. doi:10.1074/jbc.M409467200
|
[14]
|
W. J. Luo, H. Wang, H. Li, B. S. Kim, S. Shah, H. J. Lee, G. Thinakaran, T. W. Kim, G. Yu and H. Xu, “PEN-2 and APH-1 Coordinately Regulate Proteolytic Processing of Presenilin 1,” Journal of Biological Chemistry, Vol. 278, No. 10, 2003, pp. 7850-7854. doi:10.1074/jbc.C200648200
|
[15]
|
G. He, W. Luo, P. Li, C. Remmers, W. J. Netzer, J. Hendrick, K. Bettayeb, M. Flajolet, F. Gorelick, L. P. Wennogle and P. Greengard, “Gamma-Secretase Activating Protein Is a Therapeutic Target for Alzheimer’s Disease,” Nature, Vol. 467, No. 7311, 2010, pp. 95-98. doi:10.1038/nature09325
|
[16]
|
S. Zhou, H. Zhou, P. J. Walian and B. K. Jap, “CD147 Is a Regulatory Subunit of the Gamma-Secretase Complex in Alzheimer’s Disease Amyloid β-Peptide Production,” Proceedings of the National Academy of Sciences of USA, Vol. 102, No. 21, 2005, pp. 7499-7504. doi:10.1073/pnas.0502768102
|
[17]
|
F. Chen, H. Hasegawa, G. Schmitt-Ulms, T. Kawarai, C. Bohm, T. Katayama, Y. Gu, N. Sanjo, M. Glista, E. Rogaeva, Y. Wakutani, R. Pardossi-Piquard, X. Ruan, A. Tandon, F. Checler, P. Marambaud, K. Hansen, D. Westaway, P. St George-Hyslop and P. Fraser, “TMP21 is a Presenilin Complex Component That Modulates Gamma-Secretase But Not Epsilon-Secretase Activity,” Nature, Vol. 440, No. 7088, 2006, pp. 1208-1212. doi:10.1038/nature04667
|
[18]
|
A. F. Kreft, R. Martone and A. Porte, “Recent Advances in the Identification of Gamma-Secretase Inhibitors to Clinically Test the Aβ Oligomer Hypothesis of Alzheimer’s Disease,” Journal of Medicinal Chemistry, Vol. 52, No. 20, 2009, pp. 6169-6188. doi:10.1021/jm900188z
|
[19]
|
M. Pettersson, G. W. Kauffman, C. W. am Ende, N. C. Patel, C. Stiff, T. P. Tran and D. S. Johnson, “Novel Gamma-Secretase Modulators: A Review of Patents from 2008 to 2010,” Expert Opinion on Therapeutic Patents, Vol. 21, No. 2, 2011, pp. 205-226.
|
[20]
|
T. A. Lanz, M. J. Karmilowicz, K. M. Wood, N. Pozdnyakov, P. Du, M. A. Piotrowski, T. M. Brown, C. E. Nolan, K. E. Richter, J. E. Finley, Q. Fei, C. F. Ebbinghaus, Y. L. Chen, D. K. Spracklin, B. Tate, K. F. Geoghegan, L. F. Lau, D. D. Auperin and J. B. Schachter, “Concentration-Dependent Modulation of Amyloid-β in Vivo and in Vitro Using the Gamma-Secretase Inhibitor, LY-450139,” Journal of Pharmacology and Experimental Therapeutics, Vol. 319, No. 2, 2006, pp. 924-933. doi:10.1124/jpet.106.110700
|
[21]
|
E. Siemers, M. Skinner, R. A. Dean, C. Gonzales, J. Satterwhite, M. Farlow, D. Ness and P. C. May, “Safety, Tolerability, and Changes in Amyloid β Concentrations after Administration of a Gamma-Secretase Inhibitor in Volunteers,” Clinical Neuropharmacology, Vol. 28, No. 3, 2005, pp. 126-132. doi:10.1097/01.wnf.0000167360.27670.29
|
[22]
|
A. Haapasalo and D. M. Kovacs, “The Many Substrates of Presenilin/Gamma-Secretase,” Journal of Alzheimer’s Disease, Vol. 25, No. 1, 2011, pp. 3-28.
|
[23]
|
B. P. Imbimbo, F. Panza, V. Frisardi, V. Solfrizzi, G. D’Onofrio, G. Logroscino, D. Seripa and A. Pilotto, “Therapeutic Intervention for Alzheimer’s Disease with Gamma-Secretase Inhibitors: Still a Viable Option?,” Expert Opinion on Investigational Drugs, Vol. 20, No. 3, 2011, pp. 325-341.
|
[24]
|
F. Panza, V. Frisardi, B. P. Imbimbo, C. Capurso, G. Logroscino, D. Sancarlo, D. Seripa, G. Vendemiale, A. Pilotto and V. Solfrizzi, “Review: Gamma-Secretase Inhibitors for the Treatment of Alzheimer’s Disease: The Current State,” CNS Neuroscience & Therapeutics, Vol. 16, No. 5, 2010, pp. 272-284. doi:10.1111/j.1755-5949.2010.00164.x
|
[25]
|
S. Demehri, A. Turkoz and R. Kopan, “Epidermal Notch1 Loss Promotes Skin Tumorigenesis by Impacting the Stromal Microenvironment,” Cancer Cell, Vol. 16, No. 1, 2009, pp. 55-66. doi:10.1016/j.ccr.2009.05.016
|
[26]
|
K. W. Gillman, J. E. Starrett Jr., M. F. Parker, K. Xie, J. J. Bronson, L. R. Marcin, K. E. McElhone, C. P. Bergstrom, R. A. Mate, R. Williams, J. E. Meredith Jr., C. R. Burton, D. M. Barten, J. H. Toyn, S. B. Roberts, K. A. Lentz, J. G. Houston, R. Zaczek, C. F. Albright, C. P. Decicco, J. E. Macor and R. E. Olson, “Discovery and Evaluation of BMS-708163, a Potent, Selective and Orally Bioavailable Gamma-Secretase Inhibitor,” ACS Medicinal Chemistry Letters, Vol. 1, No. 3, 2010, pp. 120-124. doi:10.1021/
|
[27]
|
J. Starrett, J. E., K. W. Gillman and R. E. Olson, “Novel Alpha-(N-Sulfonamido)Acetamide Compound as an Inhibitor of Beta Amyloid Peptide Production,” U.S. Patent No. 2009/0227642 A0227641, 2009.
|
[28]
|
S. Weggen, J. L. Eriksen, P. Das, S. A. Sagi, R. Wang, C. U. Pietrzik, K. A. Findlay, T. E. Smith, M. P. Murphy, T. Bulter, D. E. Kang, N. Marquez-Sterling, T. E. Golde and E. H. Koo, “A Subset of NSAIDs Lower Amyloidogenic Aβ42 Independently of Cyclooxygenase Activity,” Nature, Vol. 414, No. 6860, 2001, pp. 212-216. doi:10.1038/35102591
|
[29]
|
M. Z. Kounnas, A. M. Danks, S. Cheng, C. Tyree, E. Ackerman, X. Zhang, K. Ahn, P. Nguyen, D. Comer, L. Mao, C. Yu, D. Pleynet, P. J. Digregorio, G. Velicelebi, K. A. Stauderman, W. T. Comer, W. C. Mobley, Y. M. Li, S. S. Sisodia, R. E. Tanzi and S. L. Wagner, “Modulation of Gamma-Secretase Reduces β-Amyloid Deposition in a Transgenic Mouse Model of Alzheimer’s Disease,” Neuron, Vol. 67, No. 5, 2010, pp. 769-780. doi:10.1016/j.neuron.2010.08.018
|
[30]
|
S. Weggen, J. L. Eriksen, S. A. Sagi, C. U. Pietrzik, T. E. Golde and E. H. Koo, “Aβ42-Lowering Nonsteroidal AntiInflammatory Drugs Preserve Intramembrane Cleavage of the Amyloid Precursor Protein (APP) and ErbB-4 Recep- tor and Signaling through the APP Intracellular Domain,” Journal of Biological Chemistry, Vol. 278, No. 33, 2003, pp. 30748-30754. doi:10.1074/jbc.M304824200
|
[31]
|
D. Oehlrich, D. J. Berthelot and H. J. Gijsen, “Gamma-Secretase Modulators as Potential Disease Modifying Anti-Alzheimer’s Drugs,” Journal of Medicinal Chemis- try, Vol. 54, No. 2011, pp. 669-698.
|
[32]
|
R. M. Page, K. Baumann, M. Tomioka, B. I. Perez- Revuelta, A. Fukumori, H. Jacobsen, A. Flohr, T. Luebbers, L. Ozmen, H. Steiner and C. Haass, “Generation of Aβ38 and Aβ42 is Independently and Differentially Affected by Familial Alzheimer Disease-Associated Presenilin Muta- tions and Gamma-Secretase Modulation,” Journal of Biological Chemistry, Vol. 283, No. 2, 2008, pp. 677-683. doi:10.1074/jbc.M708754200
|
[33]
|
J. C. Hannam, J. J. Kulagowski, A. Madin, M. P. Ridgill and E. M. Steward, “Preparation of Piperidines and Related Compounds for Treatment of Alzheimer’s Disease,” International Patent No. WO2006/043064, 2006.
|
[34]
|
T. Kimura, N. Kitazawa, T. Kaneko, N. Sato, K. Kawano, K. Ito, M. Takaishi, T. Sasaki, Y. Yoshida, T. Uemura, T. Doko, D. Shinmyo, D. Hasegawa, T. Miyagawa and H. Hagiwara, “Multi-Cyclic Compounds,” U.S. Patent No. 2009/0062529 A0062521, 2009.
|
[35]
|
Y. M. Li, M. T. Lai, M. Xu, Q. Huang, J. DiMuzio-Mower, M. K. Sardana, X. P. Shi, K. C. Yin, J. A. Shafer and S. J. Gardell, “Presenilin 1 Is Linked with Gamma-Secretase Activity in the Detergent Solubilized State,” Proceedings of the National Academy of Sciences of USA, Vol. 97, No. 11, 2000, pp. 6138-6143. doi:10.1073/pnas.110126897
|
[36]
|
W. T. Kimberly, W. P. Esler, W. Ye, B. L. Ostaszewski, J. Gao, T. Diehl, D. J. Selkoe and M. S. Wolfe, “Notch and the Amyloid Precursor Protein Are Cleaved by Similar Gamma-Secretase(s),” Biochemistry, Vol. 42, No. 1, 2003, pp. 137-144. doi:10.1021/bi026888g
|
[37]
|
D. L. Miller, A. Potempska and P. D. Mehta, “Humoral Immune Responses to Peptides Derived from the β- Amyloid Peptide C-Terminal Sequence,” Amyloid, Vol. 14, No. 1, 2007, pp. 39-50.
|
[38]
|
J. Franberg, H. Welander, M. Aoki, B. Winblad, L. O. Tjernberg and S. Frykman, “Rat Brain Gamma-Secretase Activity Is Highly Influenced By Detergents,” Biochemistry, Vol. 46, No. 25, 2007, pp. 7647-7654. doi:10.1021/bi0621258
|
[39]
|
J. Hawkins, D. C. Harrison, S. Ahmed, R. P. Davis, T. Chapman, I. Marshall, B. Smith, T. L. Mead, A. Medhurst, G. M. Giblin, A. Hall, M. I. Gonzalez, J. Richardson and I. Hussain, “Dynamics of Aβ42 Reduction in Plasma, CSF and Brain of Rats Treated with the Gamma-Secretase Modulator, GSM-10h,” Neurodegenerative Diseases, Vol. 8, No. 6, 2011, pp. 455-464. doi:10.1159/000324511
|
[40]
|
B. Van Broeck, J. M. Chen, G. Treton, M. Desmidt, C. Hopf, N. Ramsden, E. Karran, M. Mercken and A. Rowley, “Chronic Treatment with a Novel Gamma-Secretase Modulator, JNJ-40418677, Inhibits Amyloid Plaque Formation in a Mouse Model of Alzheimer’s Disease,” British Journal of Pharmacology, Vol. 163, No. 2, 2011, pp. 375-389. doi:10.1111/j.1476-5381.2011.01207.x
|
[41]
|
E. Portelius, B. Van Broeck, U. Andreasson, M. K. Gustavsson, M. Mercken, H. Zetterberg, H. Borghys and K. Blennow, “Acute Effect on the Aβ Isoform Pattern in CSF in Response to Gamma-Secretase Modulator and Inhibitor Treatment in Dogs,” Journal of Alzheimer’s Disease, Vol. 21, No. 3, 2010, pp. 1005-1012.
|
[42]
|
R. Wang, B. Wang, W. He and H. Zheng, “Wild-Type Presenilin 1 Protects against Alzheimer Disease Mutation-Induced Amyloid Pathology,” Journal of Biological Chemistry, Vol. 281, No. 22, 2006, pp. 15330-15336. doi:10.1074/jbc.M512574200
|
[43]
|
J. L. Goggi, H. D. Lewis, J. Mok, T. Harrison, M. S. Shearman, J. R. Atack and J. D. Best, “A Comparative Assessment of Gamma-Secretase Activity in Transgenic and Non-Transgenic Rodent Brain,” Journal of Neuroscience Methods, Vol. 157, No. 2, 2006, pp. 246-252. doi:10.1016/j.jneumeth.2006.05.001
|
[44]
|
J. Y. Hur, H. Welander, H. Behbahani, M. Aoki, J. Franberg, B. Winblad, S. Frykman and L. O. Tjernberg, “Active Gamma-Secretase Is Localized to Detergent-Resistant Membranes in Human Brain,” FEBS Journal, Vol. 275, No. 6, 2008, pp. 1174-1187. doi:10.1111/j.1742-4658.2008.06278.x
|
[45]
|
G. Thinakaran, D. R. Borchelt, M. K. Lee, H. H. Slunt, L. Spitzer, G. Kim, T. Ratovitsky, F. Davenport, C. Nordstedt, M. Seeger, J. Hardy, A. I. Levey, S. E. Gandy, N. A. Jenkins, N. G. Copeland, D. L. Price and S. S. Sisodia, “Endoproteolysis of Presenilin 1 and Accumulation of Processed Derivatives in Vivo,” Neuron, Vol. 17, No. 1, 1996, pp. 181-190. doi:10.1016/S0896-6273(00)80291-3
|
[46]
|
A. Ebke, T. Luebbers, A. Fukumori, K. Shirotani, C. Haass, K. Baumann and H. Steiner, “Novel Gamma-Secretase Modulators Directly Target Presenilin,” Journal of Biological Chemistry, Vol. 286, 2011, pp. 37181-37186.
|
[47]
|
C. J. Crump, B. A. Fish, S. V. Castro, D.-M. Chau, N. Gertsik, K. Ahn, C. Stiff, N. Pozdnyakov, K. R. Bales, D. S. Johnson and Y.-M. Li, “Piperidine Acetic Acid Based Gamma-Secretase Modulators Directly Bind to Presenilin-1,” ACS Chemical Neuroscience, Vol. 2, No. 12, 2011, pp. 705-710.
|
[48]
|
B. De Strooper and W. Annaert, “Novel Research Horizons for Presenilins and Gamma-Secretases in Cell Biology and Disease,” Annual Review of Cell and Developmental Biology, Vol. 26, 2010, pp. 235-260. doi:10.1146/annurev-cellbio-100109-104117
|
[49]
|
T. Wakabayashi, K. Craessaerts, L. Bammens, M. Bentahir, F. Borgions, P. Herdewijn, A. Staes, E. Timmerman, J. Vandekerckhove, E. Rubinstein, C. Boucheix, K. Gevaert and B. De Strooper, “Analysis of the Gamma-Secretase Interactome and Validation of Its Association with Tetraspanin-Enriched Microdomains,” Nature Cell Biology, Vol. 11, No. 11, 2009, pp. 1340-1346. doi:10.1038/ncb1978
|