- About this Journal ·
- Abstracting and Indexing ·
- Aims and Scope ·
- Annual Issues ·
- Article Processing Charges ·
- Author Guidelines ·
- Bibliographic Information ·
- Citations to this Journal ·
- Contact Information ·
- Editorial Board ·
- Editorial Workflow ·
- Free eTOC Alerts ·
- Publication Ethics ·
- Recently Accepted Articles ·
- Reviewers Acknowledgment ·
- Submit a Manuscript ·
- Subscription Information ·
- Table of Contents
International Journal of Alzheimer’s Disease
Volume 2012 (2012), Article ID 210756, 10 pages
Modulation of Gamma-Secretase for the Treatment of Alzheimer's Disease
Satori Pharmaceuticals, Inc., 281 Albany Street, Cambridge, MA 02139, USA
Received 13 August 2012; Accepted 8 November 2012
Academic Editor: Jeremy Toyn
Copyright © 2012 Barbara Tate et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
- N. Kakuda, S. Funamoto, S. Yagishita et al., “Equimolar production of amyloid β-protein and amyloid precursor protein intracellular domain from β-carboxyl-terminal fragment by γ-secretase,” Journal of Biological Chemistry, vol. 281, no. 21, pp. 14776–14786, 2006.
- T. Sato, N. Dohmae, Y. Qi et al., “Potential link between amyloid β-protein 42 and C-terminal fragment γ 49-99 of β-amyloid precursor protein,” Journal of Biological Chemistry, vol. 278, no. 27, pp. 24294–20301, 2003.
- Y. Qi-Takahara, M. Morishima-Kawashima, Y. Tanimura et al., “Longer forms of amyloid β protein: implications for the mechanism of intramembrane cleavage by γ-secretase,” Journal of Neuroscience, vol. 25, no. 2, pp. 436–445, 2005.
- M. Takami, Y. Nagashima, Y. Sano et al., “γ-Secretase: successive tripeptide and tetrapeptide release from the transmembrane domain of β-carboxyl terminal fragment,” Journal of Neuroscience, vol. 29, no. 41, pp. 13042–13052, 2009.
- T. E. Golde, Y. Ran, and K. M. Felsenstein, “Shifting a complex debate on γ-secretase cleavage and Alzheimer's disease,” The EMBO Journal, vol. 31, no. 10, pp. 2237–2239, 2012.
- N. Suzuki, T. T. Cheung, X. D. Cai et al., “An increased percentage of long amyloid β protein secreted by familial amyloid β protein precursor (βAPP717) mutants,” Science, vol. 264, no. 5163, pp. 1336–1340, 1994.
- T. Saito, T. Suemoto, N. Brouwers et al., “Potent amyloidogenicity and pathogenicity of Aβ 243,” Nature Neuroscience, vol. 14, no. 8, pp. 1023–1032, 2011.
- 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, pp. 4693–4697, 1993.
- J. Milano, J. McKay, C. Dagenais et al., “Modulation of Notch processing by γ-secretase inhibitors causes intestinal goblet cell metaplasia and induction of genes known to specify gut secretory lineage differentiation,” Toxicological Sciences, vol. 82, no. 1, pp. 341–358, 2004.
- G. H. Searfoss, W. H. Jordan, D. O. Calligaro et al., “Adipsin, a biomarker of gastrointestinal toxicity mediated by a functional γ-secretase inhibitor,” Journal of Biological Chemistry, vol. 278, no. 46, pp. 46107–46116, 2003.
- G. T. Wong, D. Manfra, F. M. Poulet et al., “Chronic treatment with the γ-secretase inhibitor LY-411,575 inhibits γ-amyloid peptide production and alters lymphopoiesis and intestinal cell differentiation,” Journal of Biological Chemistry, vol. 279, no. 13, pp. 12876–12882, 2004.
- E. Lilly, “Lilly Halts Development of Semagacestat for Alzheimer's Disease Based on Preliminary Results of Phase III Clinical Trials,” 2010, http://newsroom.lilly.com/releasedetail.cfm?releaseid=499794.
- D. J. Selkoe, “Resolving controversies on the path to Alzheimer's therapeutics,” Nature Medicine, vol. 17, no. 9, pp. 1060–1065, 2011.
- B. P. Imbimbo, F. Panza, V. Frisardi et al., “Therapeutic intervention for Alzheimer's disease with γ-secretase inhibitors: still a viable option?” Expert Opinion on Investigational Drugs, vol. 20, no. 3, pp. 325–341, 2011.
- S. Weggen, J. L. Eriksen, P. Das et al., “A subset of NSAIDs lower amyloidogenic Aβ42 independently of cyclooxygenase activity,” Nature, vol. 414, no. 6860, pp. 212–216, 2001.
- T. E. Golde, L. S. Schneider, and E. H. Koo, “Anti-Aβ therapeutics in alzheimer's disease: the need for a paradigm shift,” Neuron, vol. 69, no. 2, pp. 203–213, 2011.
- B. P. Imbimbo, “Why did tarenflurbil fail in alzheimer's disease?” Journal of Alzheimer's Disease, vol. 17, no. 4, pp. 757–760, 2009.
- R. C. Green, L. S. Schneider, D. A. Amato et al., “Effect of tarenflurbil on cognitive decline and activities of daily living in patients with mild Alzheimer disease: a randomized controlled trial,” Journal of the American Medical Association, vol. 302, no. 23, pp. 2557–2564, 2009.
- B. Bulic, J. Ness, S. Hahn, A. Rennhack, T. Jumpertz, and S. Weggen, “Chemical biology, molecular mechanism and clinical perspective of γ-secretase modulators in Alzheimer's disease,” Current Neuropharmacology, vol. 9, no. 4, pp. 598–622, 2011.
- J. L. Hubbs, N. O. Fuller, W. F. Austin et al., “Optimization of a natural product-based class of gamma-secretase modulators,” Journal of Medicinal Chemistry, vol. 55, no. 21, pp. 9270–9282, 2012.
- E. H. M. Koo, T. E. Golde, and D. R. Galasko, “Nonsteroidal antiinflammatory drug (NSAID) and NSAID derivative amyloid Aβ42 polypeptide-lowering agents for the treatment of Alzheimer's disease, and screening methods,” pp. 73, Mayo Foundation for Medical Education and Research, USA, 2001.
- L. Raveglia, I. Peretto, S. Radaelli, B. P. Imbimbo, A. Rizzi, and G. Villetti, “Preparation of 1-phenylalkanecarboxylic acid derivatives for the treatment of neurodegenerative diseases,” pp. 91, Chiesi Farmaceutici S.p.A., Italy, 2004.
- P. Blurton, et al., “Arylacetic acids and related compounds and their preparation, pharmaceutical compositions and their use for treatment of diseases associated with the deposition of β-amyloid peptides in the brain such as Alzheimer's disease,” pp. 58, Merck Sharp & Dohme Limited, UK, 2006.
- C. Y. Ho, Preparation of Biphenyl Derivatives as γ-secretAse Modulators, Janssen Pharmaceutica, Belg, Germany, 2009.
- F. Wilson, A. Reid, V. Reader, et al., “Preparation of biphenylacetic acids as γ-secretase modulators for the treatment of Alzheimer's disease,” pp. 57, Cellzome, Germany, 2006.
- G. Shapiro and R. Chesworth, “1,3,4-Trisubstituted benzenes as γ-secretase inhibitors and their preparation and use in the treatment of neurodegenerative diseases,” pp. 165, Envivo Pharmaceuticals, USA, 2009.
- J. J. Kulagowski, A. Madin, P. M. Ridgill, and M. E. Seward, “Preparation of piperidines and related compounds for treatment of Alzheimer's disease,” pp. 178, Merck Sharp & Dohme Limited, UK, 2006.
- A. Hall, R. L. Elliott, G. M. P. Giblin et al., “Piperidine-derived γ-secretase modulators,” Bioorganic and Medicinal Chemistry Letters, vol. 20, no. 3, pp. 1306–1311, 2010.
- E. C. W. Am, et al., “Aminocyclohexanes and aminotetrahydropyrans as γ-secretase modulators and their preparation and use for thetreatment of neurological and psychiatric diseases,” pp. 91, Pfizer, USA, 2011.
- S. Cheng, D. D. Comer, L. Mao, G. P. Balow, and D. Pleynet, “Aryl compounds and uses in modulating amyloid β,” pp. 178, Neurogenetics, USA 2004.
- K. Baumann, et al., “Preparation of thiazolyl-substituted imidazolylphenylamine derivatives and related compounds as modulators of amyloid beta,” pp. 32, Hoffmann-La Roche, USA, 2008.
- L. R. Marcin, et al., “Preparation of bicyclic compounds, especially bicyclic triazoles, for the reduction of beta-amyloid protein production,” pp. 242, Bristol-Myers Squibb Company, USA, 2010.
- R. Forsblom, K. Paulsen, M. Waldman, D. Rotticci, and E. Santangelo, “Preparation of 2-aminopyrimidines as amyloid beta modulators,” pp. 227, AstraZeneca AB, Sweden, 2010.
- K. Biswas, J. J. Chen, J. R. Falsey, et al., “Preparation of urea compounds as gamma secretase modulators,” pp. 116, Amgen, USA, 2009.
- H. J. M. Gijsen, A. I. Velter, G. J. MacDonald, et al., “Novel substituted bicyclic heterocyclic compounds as gamma secretase modulators and their preparation and use in the treatment of diseases,” pp. 164, Ortho-Mcneil-Janssen Pharmaceuticals, USA, 2010.
- P. Blurton, et al., “Preparation of heteroarylpiperazine derivatives for use in treatment of Alzheimer's disease,” pp.68, Merck & Co., Merck Sharp & Dohme Limited, USA, 2008.
- M. A. Findeis, F. Schroeder, T. D. McKee et al., “Discovery of a novel pharmacological and structural class of gamma secretase modulators derived from the extract of actaea racemosa,” ACS Chemical Neuroscience, vol. 3, no. 11, pp. 941–951, 2012.
- S. J. Haugabook, D. M. Yager, E. A. Eckman, T. E. Golde, S. G. Younkin, and C. B. Eckman, “High throughput screens for the identification of compounds that alter the accumulation of the Alzheimer's amyloid β peptide (Aβ),” Journal of Neuroscience Methods, vol. 108, no. 2, pp. 171–179, 2001.
- M. P. Murphy, S. N. Uljon, P. E. Fraser et al., “Presenilin 1 regulates pharmacologically distinct γ-secretase activities: implications for the role of presenilin in γ-secretase cleavage,” Journal of Biological Chemistry, vol. 275, no. 34, pp. 26277–26284, 2000.
- T. A. Lanz, M. J. Karmilowicz, K. M. Wood et al., “Concentration-dependent modulation of amyloid-β in vivo and in vitro using the γ-secretase inhibitor, LY-450139,” Journal of Pharmacology and Experimental Therapeutics, vol. 319, no. 2, pp. 924–933, 2006.
- K. Rogers, et al., “Optimization of a natural product-based class of gamma secretase modulators,” in International Conference on Alzheimer's Disease, Vienna, Austria, 2009.
- C. R. Burton, J. E. Meredith, D. M. Barten et al., “The amyloid-β rise and γ-secretase inhibitor potency depend on the level of substrate expression,” Journal of Biological Chemistry, vol. 283, no. 34, pp. 22992–23003, 2008.
- J. D. Hughes, J. Blagg, D. A. Price et al., “Physiochemical drug properties associated with in vivo toxicological outcomes,” Bioorganic and Medicinal Chemistry Letters, vol. 18, no. 17, pp. 4872–4875, 2008.
- T. T. Wager, X. Hou, P. R. Verhoest, and A. Villalobos, “Moving beyond rules: the development of a central nervous system multiparameter optimization (CNS MPO) approach to enable alignment of druglike properties,” ACS Chemical Neuroscience, vol. 1, no. 6, pp. 435–449, 2010.
- T. T. Wager, R. Y. Chandrasekaran, X. Hou et al., “Defining desirable central nervous system drug space through the alignment of molecular properties, in vitro ADME, and safety attributes,” ACS Chemical Neuroscience, vol. 1, no. 6, pp. 420–434, 2010.
- F. Lovering, J. Bikker, and C. Humblet, “Escape from flatland: increasing saturation as an approach to improving clinical success,” Journal of Medicinal Chemistry, vol. 52, no. 21, pp. 6752–6756, 2009.
- T. J. Ritchie and S. J. F. Macdonald, “The impact of aromatic ring count on compound developability—are too many aromatic rings a liability in drug design?” Drug Discovery Today, vol. 14, no. 21-22, pp. 1011–1020, 2009.
- T. Kimura, K. Kawano, E. Doi, et al., “Preparation of cinnamide, 3-benzylidenepiperidin-2-one, phenylpropynamide compounds as amyloid β production inhibitors,” pp. 679, Eisai, Japan, 2005.
- A. Ebke, T. Luebbers, A. Fukumori et al., “Novel γ-secretase enzyme modulators directly target presenilin protein,” Journal of Biological Chemistry, vol. 286, pp. 37181–37186, 2011.
- M. S. Wolfe, “gamma-Secretase inhibitors and modulators for Alzheimer's disease,” Journal of Neurochemistry, vol. 120, supplement 1, pp. 89–98, 2012.
- Y. Ohki, T. Higo, K. Uemura et al., “Phenylpiperidine-type γ-secretase modulators target the transmembrane domain 1 of presenilin 1,” The EMBO Journal, vol. 30, no. 23, pp. 4815–4824, 2011.
- S. Weggen and D. Beher, “Molecular consequences of amyloid precursor protein and presenilin mutations causing autosomal-dominant Alzheimer's disease,” Alzheimer's Research and Therapy, vol. 4, no. 2, Article ID 9, 2012.
- K. Takeo, N. Watanabe, T. Tomita, and T. Iwatsubo, “Contribution of the γ-secretase subunits to the formation of catalytic pore of presenilin 1 protein,” Journal of Biological Chemistry, vol. 287, no. 31, pp. 25834–25843, 2012.