Moderate reduction of γ-secretase: Is there a therapeutic sweet spot?

Journal of Neuroscience

Volumn 27, Issue 50, 2007, Pages 13579-13580

  Se, Hoon Choi ^a   Norstrom, Eric ^a  

^a UNIVERSITY OF CHICAGO   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AMYLOID BETA PROTEIN; AMYLOID PRECURSOR PROTEIN; GAMMA SECRETASE; NOTCH RECEPTOR;

ADVERSE OUTCOME; ALZHEIMER DISEASE; BIOACCUMULATION; COGNITION; EMBRYO CELL; ENZYME ACTIVITY; ENZYME INHIBITION; ENZYME MECHANISM; ENZYME SUBSTRATE; EXPERIMENTAL MODEL; EXPERIMENTAL MOUSE; IMMUNOHISTOCHEMISTRY; NONHUMAN; NOTE; PATHOPHYSIOLOGY; PRIORITY JOURNAL; PROTEIN FUNCTION; PROTEIN LOCALIZATION; REDUCTION; RISK ASSESSMENT; TREATMENT INDICATION; WILD TYPE;

ALZHEIMER DISEASE; AMYLOID BETA-PROTEIN; AMYLOID PRECURSOR PROTEIN SECRETASES; ANIMALS; BRAIN; CARCINOMA, SQUAMOUS CELL; CELLS, CULTURED; CROSSES, GENETIC; DISEASE MODELS, ANIMAL; DISEASE PROGRESSION; FIBROBLASTS; GENE EXPRESSION REGULATION; HUMANS; MICE; MICE, TRANSGENIC; SKIN NEOPLASMS; SPLENOMEGALY; SURVIVAL RATE;

EID: 37249013809     PISSN: 02706474     EISSN: 02706474     Source Type: Journal    
DOI: 10.1523/JNEUROSCI.4821-07.2007     Document Type: Note

References (9)

1. Guidos CJ (2002) Notch signaling in lymphocyte development. Semin Immunol 14:395-404.
2. Jankowsky JL, Slunt HH, Gonzales V, Savonenko AV, Wen JC, Jenkins NA, Copeland NG, Younkin LH, Lester HA, Younkin SG, Borchelt DR (2005) Persistent amyloidosis following suppression of Abeta production in a transgenic model of Alzheimer disease. PLoS Med 2:e355.
3. Lesne S, Koh MT, Kotilinek L, Kayed R, Glabe CG, Yang A, Gallagher M, Ashe KH (2006) A specific amyloid-beta protein assembly in the brain impairs memory. Nature 440:352-357.
4. Li T, Wen H, Brayton C, Laird FM, Ma G, Peng S, Placanica L, Wu TC, Crain BJ, Price DL, Eberhart CG, Wong PC (2007) Moderate reduction of gamma-secretase attenuates amyloid burden and limits mechanism-based liabilities. J Neurosci 27:10849-10859.
5. Milano J, McKay J, Dagenais C, Foster-Brown L, Pognan F, Gadient R, Jacobs RT, Zacco A, Greenberg B, Ciaccio PJ (2004) Modulation of notch processing by gamma-secretase inhibitors causes intestinal goblet cell metaplasia and induction of genes known to specify gut secretory lineage differentiation. Toxicol Sci 82:341-358.
6. Nicolas M, Wolfer A, Raj K, Kummer JA, Mill P, van Noort M, Hui CC, Clevers H, Dotto GP, Radtke F (2003) Notch1 functions as a tumor suppressor in mouse skin. Nat Genet 33:416-421.
7. Schenk D, Barbour R, Dunn W, Gordon G, Grajeda H, Guido T, Hu K, Huang J, Johnson-Wood K, Khan K, Kholodenko D, Lee M, Liao Z, Lieberburg I, Motter R, Mutter L, Soriano F, Shopp G, Vasquez N, Vandevert C, et al. (1999) Immunization with amyloid-beta attenuates Alzheimer-disease-like pathology in the PDAPP mouse. Nature 400:173-177.
8. Sisodia SS, St George-Hyslop PH (2002) gamma-Secretase, Notch, Abeta and Alzheimer's disease: where do the presenilins fit in? Nat Rev Neurosci 3:281-290.
9. Zhang L, Lee J, Song L, Sun X, Shen J, Terracina G, Parker EM (2005) Characterization of the reconstituted gamma-secretase complex from Sf9 cells co-expressing presenilin 1, nicastrin [correction of nacastrin], aph-1a, and pen-2. Biochemistry 44:4450-4457.