Substrate-targeting γ-secretase modulators

Nature

Volumn 453, Issue 7197, 2008, Pages 925-929

  Kukar, Thomas L ^a   Ladd, Thomas B ^a   Bann, Maralyssa A ^a   Fraering, Patrick C ^b,c   Narlawar, Rajeshwar ^d   Maharvi, Ghulam M ^a   Healy, Brent ^a   Chapman, Robert ^a   Welzel, Alfred T ^e   Price, Robert W ^a   Moore, Brenda ^a   Rangachari, Vijayaraghavan ^a   Cusack, Bernadette ^a   Eriksen, Jason ^a   Jansen West, Karen ^a   Verbeeck, Christophe ^a   Yager, Debra ^a   Eckman, Christopher ^a   Ye, Wenjuan ^c   Sagi, Sarah ^f   Cottrell, Barbara A ^f   Torpey, Justin ^f   Rosenberry, Terrone L ^a   Fauq, Abdul ^a   Wolfe, Michael S ^c   Schmidt, Boris ^d   Walsh, Dominic M ^e   Koo, Edward H ^f   Golde, Todd E ^a   more..

^a MAYO CLINIC   (United States)

^b EPFL   (Switzerland)

^c HARVARD MEDICAL SCHOOL   (United States)

^d DARMSTADT UNIVERSITY OF TECHNOLOGY   (Germany)

^e UNIVERSITY COLLEGE DUBLIN   (Ireland)

^f UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AMYLOID BETA PROTEIN[1-42]; AMYLOID BETA PROTEIN[25-35]; AMYLOID PRECURSOR PROTEIN; FENOFIBRATE; GAMMA SECRETASE; GAMMA SECRETASE MODULATOR; NONSTEROID ANTIINFLAMMATORY AGENT; NOTCH RECEPTOR; STREPTAVIDIN; TARENFLURBIL;

DISEASE; DRUG; ENZYME ACTIVITY; MUTATION; PEPTIDE;

ARTICLE; BIOTINYLATION; CHO CELL; CONTROLLED STUDY; DRUG INHIBITION; DRUG STRUCTURE; DRUG TARGETING; GLIOMA CELL; HUMAN; HUMAN CELL; IMMUNOPRECIPITATION; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTEIN AGGREGATION; PROTEIN LOCALIZATION;

EID: 45149105232     PISSN: 00280836     EISSN: 14764687     Source Type: Journal    
DOI: 10.1038/nature07055     Document Type: Article

References (32)

1. Kukar, T. & Golde, T. E. Possible mechanisms of action of NSAIDs and related compounds that modulate γ-secretase cleavage. Curr. Top. Med. Chem. 8, 47-53 (2008).
2. Kodadek, T. Inhibition of proteolysis and other posttranslational modifications with substrate-targeted inhibitors. Biopolymers 66, 134-140 (2002).
3. Eriksen, J. L. et al. NSAIDs and enantiomers of flurbiprofen target γ-secretase and lower Aβ 42 in vivo. J. Clin. Invest. 112, 440-449 (2003).
4. Weggen, S. et al. Asubset of NSAIDs lower amyloidogenic Aβ42 independently of cyclooxygenase activity. Nature 414, 212-216 (2001).
5. Christensen, D. D. Changing the course of Alzheimer's disease: anti-amyloid disease-modifying treatments on the horizon. Prim. Care Companion J. Clin. Psychiatry 9, 32-41 (2007).
6. Kukar, T. et al. Chronic administration of R-flurbiprofen attenuates learning impairments in transgenic amyloid precursor protein mice. BMC Neurosci. 8, 54 (2007).
7. Kukar, T. et al. Diverse compounds mimic Alzheimer disease-causing mutations by augmenting Aβ42 production. Nature Med. 11, 545-550 (2005).
8. Narlawar, R., Baumann, K., Czech, C. & Schmidt, B. Conversion of the LXR-agonist TO-901317-From inverse to normal modulation of γ-secretase by additionof a carboxylic acid and a lipophilic anchor. Bioorg. Med. Chem. Lett. 17, 5428-5431 (2007).
9. Leuchtenberger, S. et al. Inhibitors of Rho-kinase modulate amyloid-β (Aβ) secretion but lack selectivity for Aγ42. J. Neurochem. 96, 355-365 (2006).
10. Weggen, S. et al. Evidence that nonsteroidal anti-inflammatory drugs decrease amyloid γ42 production by direct modulation of γ-secretase activity. J. Biol. Chem. 278, 31831-31837 (2003).
11. Dorman, G. & Prestwich, G. D. Benzophenone photophores in biochemistry. Biochemistry 33, 5661-5673 (1994).
12. Fraering, P. C. et al. Purification and characterization of the human γ-secretase complex. Biochemistry 43, 9774-9789 (2004).
13. Narlawar, R. et al. Scaffold of the cyclooxygenase-2 (COX-2) inhibitor carprofen provides Alzheimer γ-secretasemodulators. J. Med. Chem. 49, 7588-7591 (2006).
14. Okochi, M. et al. Secretion of the Notch-1 Aβ-like peptide during Notch signaling. J. Biol. Chem. 281, 7890-7898 (2006).
15. Sagi, S. A. et al. NSAIDs Show Specificity for APP γ-Secretase Cleavage over Notch and CD44 (Society for Neuroscience, Program no. 264.10, Abstract Viewer/Itinerary Planner, Washington DC, 2004).
16. Grziwa, B. et al. The transmembrane domain of the amyloid precursor protein in microsomal membranes is on both sides shorter than predicted. J. Biol. Chem. 278, 6803-6808 (2003).
17. Sato, T. et al. Inhibitors of amyloid toxicity based on beta-sheet packing of Aβ40 and Aβ42. Biochemistry 45, 5503-5516 (2006).
18. Chen, Y.-R. & Glabe, C. G. Distinct early folding and aggregation properties of Alzheimer amyloid-β peptides Aβ40 and Aβ42. J. Biol. Chem. 281, 24414-24422 (2006).
19. Murphy, M. P. et al. c-secretase, evidence for multiple proteolytic activities and influence of membrane positioning of substrate on generation of amyloid b peptides of varying length. J. Biol. Chem. 274, 11914-11923 (1999).
20. Munter, L. M. et al. GxxxG motifs within the amyloid precursor protein transmembrane sequence are critical for the etiology of Aβ42. EMBO J. 26, 1702-1712 (2007).
21. Hirohata, M., Ono, K., Naiki, H. & Yamada, M. Non-steroidal anti-inflammatory drugs have anti-amyloidogenic effects for Alzheimer's b-amyloid fibrils in vitro. Neuropharmacology 49, 1088-1099 (2005).
22. Podlisny, M. B. et al. Oligomerization of endogenous and synthetic amyloid β-protein at nanomolar levels in cell culture and stabilization of monomer by Congo red. Biochemistry 37, 3602-3611 (1998).
23. Ferrao-Gonzales, A. D. et al. Controlling β-amyloid oligomerization by the use of naphthalene sulfonates: trapping low molecular weight oligomeric species. J. Biol. Chem. 280, 34747-34754 (2005).
24. Walsh, D. M. et al. Naturally secreted oligomers of amyloid β protein potently inhibit hippocampal long-term potentiation in vivo. Nature 416, 535-539 (2002).
25. Calabrese, B. et al. Rapid, concurrent alterations in pre- and postsynaptic structure induced by naturally-secreted amyloid-β protein. Mol. Cell. Neurosci. 35, 183-193 (2007).
26. Xia, W. et al. Enhanced production and oligomerization of the 42-residue amyloid β-protein by Chinese hamster ovary cells stably expressing mutant presenilins. J. Biol. Chem. 272, 7977-7982 (1997).
27. Walsh, D. M., Tseng, B. P., Rydel, R. E., Podlisny, M. B. & Selkoe, D. J. The oligomeriation of amyloid β protein begins intracellularly in cells derived from human brain. Biochemistry 39, 10831-10839 (2000).
28. Lleo, A. et al. Nonsteroidal anti-inflammatory drugs lower Aβ42 and change presenilin 1 conformation. Nature Med. 10, 1065-1066 (2004).
29. Beher, D. et al. Selected non-steroidal anti-inflammatory drugs and their derivatives target γ-secretase at a novel site: evidence for an allosteric mechanism. J. Biol. Chem. 279, 43419-43426 (2004).
30. Dong, D. L., Liu, R., Sherlock, R., Wigler, M. H. & Nestler, H. P. Molecular forceps from combinatorial libraries prevent the farnesylation of Ras by binding to its carboxyl terminus. Chem. Biol. 6, 133-141 (1999).
31. De Ferrari, G. V., Mallender, W. D., Inestrosa, N. C. &Rosenberry, T. L. Thioflavin T is a fluorescent probe of the acetylcholinesterase peripheral site that reveals conformational interactions between the peripheral and acylation Sites. J. Biol. Chem. 276, 23282-23287 (2001).
32. Johnson, J. L., Cusack, B., Davies, M. P., Fauq, A. & Rosenberry, T. L. Unmasking tandem site interaction in human acetylcholinesterase. Substrate activation with a cationic acetanilide substrate. Biochemistry 42, 5438-5452 (2003).