Discovery of notch-sparing γ-secretase inhibitors

Current Alzheimer Research

Volumn 7, Issue 3, 2010, Pages 207-209

  Augelli Szafran, C E ^a   Wei, H X ^a   Lu, D ^a   Zhang, J ^a   Gu, Y ^a   Yang, T ^a   Osenkowski, P ^a   Ye, W ^a   Wolfe, M S ^a  

^a BRIGHAM AND WOMEN S HOSPITAL   (United States)

Author keywords

Amyloid; Drug discovery; Inhibitors; Protease

Indexed keywords

AMYLOID BETA PROTEIN; GAMMA SECRETASE; IMATINIB; NOTCH RECEPTOR; PROTEINASE;

ALZHEIMER DISEASE; ARTICLE; DRUG EFFECT; DRUG INHIBITION; DRUG LABELING; DRUG TARGETING; IC 50; LIPOPHILICITY; NONHUMAN; PHYSICAL CHEMISTRY; PRIORITY JOURNAL; PROTEIN DEGRADATION;

ALZHEIMER DISEASE; AMYLOID BETA-PROTEIN; AMYLOID PRECURSOR PROTEIN SECRETASES; ANIMALS; DISEASE MODELS, ANIMAL; DRUG DESIGN; DRUG EVALUATION, PRECLINICAL; ENZYME INHIBITORS; HUMANS; MOLECULAR STRUCTURE; RECEPTORS, NOTCH; SIGNAL TRANSDUCTION;

EID: 77952534139     PISSN: 15672050     EISSN: None     Source Type: Journal    
DOI: 10.2174/156720510791050920     Document Type: Article

References (10)

1. Wolfe MS. The gamma-secretase complex: membrane-embedded proteolytic ensemble. Biochemistry 45(26): 7931-7939 (2006).
2. Kopan R, Ilagan MX. Gamma-secretase: proteasome of the membrane? Nat Rev Mol Cell Biol 5(6): 499-504 (2004).
3. Searfoss GH, Jordan WH, Calligaro DO, Galbreath EJ, Schirtzinger LM, Berridge BR, et al. Adipsin: a biomarker of gastrointestinal toxicity mediated by a functional gamma secretase inhibitor. J Biol Chem 278: 46107-46116 (2003).
4. Wong GT, Manfra D, Poulet FM, Zhang Q, Josien H, Bara T, et al. Chronic treatment with the gamma-secretase inhibitor LY-411,575 inhibits beta-amyloid peptide production and alters lymphopoiesis and intestinal cell differentiation. J Biol Chem 279(13): 12876-12882 (2004).
5. Weggen S, Eriksen JL, Das P, Sagi SA, Wang R, Pietrzik CU, et al. A subset of NSAIDs lower amyloidogenic Abeta42 independently of cyclooxygenase activity. Nature 414(6860): 212-216 (2001).
6. Weggen S, Eriksen JL, Sagi SA, Pietrzik CU, Ozols V, Fauq A, et al. Evidence that nonsteroidal anti-inflammatory drugs decrease amyloid beta 42 production by direct modulation of gammasecretase activity. J Biol Chem 278(34): 31831-31837 (2003).
7. Zhou Y, Su Y, Li B, Liu F, Ryder JW, Wu X, et al. Nonsteroidal anti-inflammatory drugs can lower amyloidogenic Abeta42 by inhibiting Rho. Science 302(5648): 1215-1217 (2003).
8. Kukar TL, Ladd TB, Bann MA, Fraering PC, Narlawar R, Maharvi GM, et al. Substrate-targeting gamma-secretase modulators. Nature 453(7197): 925-929 (2008).
9. Netzer WJ, Dou F, Cai D, Veach D, Jean S, Li Y, et al. Gleevec inhibits beta-amyloid production but not Notch cleavage. Proc Natl Acad Sci USA 100(21): 12444-12449 (2003).
10. Fraering PC, Ye W, Lavoie MJ, Ostaszewski BL, Selkoe DJ, Wolfe MS. gamma -Secretase substrate selectivity can be modulated directly via interaction with a nucleotide binding site. J Biol Chem 280: 41987-41996 (2005).