MEK inhibitors suppress β-amyloid production by altering the level of a β-C-terminal fragment of amyloid precursor protein in neuronal cells

FEBS Letters

Volumn 584, Issue 15, 2010, Pages 3410-3414

  Araki, Wataru ^a   Kametani, Fuyuki ^b   Oda, Akiko ^a,c   Tamaoka, Akira ^c  

^a NATIONAL INSTITUTE OF NEUROSCIENCE   (Japan)

^b TOKYO METROPOLITAN INSTITUTE OF MEDICAL SCIENCE   (Japan)

^c UNIVERSITY OF TSUKUBA   (Japan)

Author keywords

Amyloid; Alzheimer's disease; Amyloid precursor protein; MEK inhibitor; Neuroblastoma; Proteasome

Indexed keywords

1,4 DIAMINO 1,4 BIS(2 AMINOPHENYLTHIO) 2,3 DICYANOBUTADIENE; 2 (2 CHLORO 4 IODOANILINO) N CYCLOPROPYLMETHOXY 3,4 DIFLUOROBENZAMIDE; AMYLOID BETA PROTEIN; AMYLOID BETA PROTEIN[1-40]; AMYLOID BETA PROTEIN[1-42]; AMYLOID PRECURSOR PROTEIN; BETA SECRETASE; GAMMA SECRETASE; MITOGEN ACTIVATED PROTEIN KINASE INHIBITOR; PROTEASOME;

ARTICLE; CARBOXY TERMINAL SEQUENCE; CONTROLLED STUDY; HUMAN; HUMAN CELL; NERVE CELL; NEUROBLASTOMA CELL; PRIORITY JOURNAL; PROTEIN DEGRADATION; PROTEIN EXPRESSION; PROTEIN SECRETION; PROTEIN SYNTHESIS INHIBITION;

AMYLOID BETA-PROTEIN PRECURSOR; AMYLOID PRECURSOR PROTEIN SECRETASES; BENZAMIDES; BUTADIENES; CELL LINE, TUMOR; HUMANS; MITOGEN-ACTIVATED PROTEIN KINASE KINASES; NEURONS; NITRILES; PROTEASOME ENDOPEPTIDASE COMPLEX; PROTEIN KINASE INHIBITORS; SIGNAL TRANSDUCTION;

EID: 77955278756     PISSN: 00145793     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.febslet.2010.06.038     Document Type: Article

References (16)

1. Hardy J., Selkoe D.J. The amyloid hypothesis of Alzheimer's disease: progress and problems on the road to therapeutics. Science 2002, 297:353-356.
2. Citron M. Beta-secretase inhibition for the treatment of Alzheimer's disease - promise and challenge. Trends Pharmacol. Sci. 2004, 25:92-97.
3. Selkoe D.J., Wolfe M.S. Presenilin: running with scissors in the membrane. Cell 2007, 131:215-221.
4. Araki W., Kume H., Oda A., Tamaoka A., Kametani F. IGF-1 promotes beta-amyloid production by a secretase-independent mechanism. Biochem. Biophys. Res. Commun. 2009, 380:111-114.
5. Takeda K., Araki W., Tabira T. Enhanced generation of intracellular Abeta42 amyloid peptide by mutation of presenilins PS1 and PS2. Eur. J. Neurosci. 2004, 19:258-264.
6. Kametani F., Tanaka K., Ishii T., Ikeda S., Kennedy H.E., Allsop D. Secretory form of Alzheimer amyloid precursor protein 695 in human brain lacks beta/A4 amyloid immunoreactivity. Biochem. Biophys. Res. Commun. 1993, 191:392-398.
7. Araki W., Yuasa K., Takeda S., Takeda K., Shirotani K., Takahashi K., Tabira T. Pro-apoptotic effect of presenilin 2 (PS2) overexpression is associated with down-regulation of Bcl-2 in cultured neurons. J. Neurochem. 2001, 79:1161-1168.
8. Kume H., Murayama K.S., Araki W. The two-hydrophobic domain tertiary structure of reticulon proteins is critical for modulation of beta-secretase BACE1. J. Neurosci. Res. 2009, 87:2963-2972.
9. Favata M.F., Horiuchi K.Y., Manos E.J., Daulerio A.J., Stradley D.A., Feeser W.S., Van Dyk D.E., Pitts W.J., Earl R.A., Hobbs F., Copeland R.A., Magolda R.L., Scherle P.A., Trzaskos J.M. Identification of a novel inhibitor of mitogen-activated protein kinase kinase. J. Biol. Chem. 1998, 273:18623-18632.
10. Sebolt-Leopold J.S., Dudley D.T., Herrera R., Van Becelaere K., Wiland A., Gowan R.C., Tecle H., Barrett S.D., Bridges A., Przybranowski S., Leopold W.R., Saltiel A.R. Blockade of the MAP kinase pathway suppresses growth of colon tumors in vivo. Nat. Med. 1999, 5:810-816.
11. Dovey H.F., John V., Anderson J.P., Chen L.Z., de Saint Andrieu P., Fang L.Y., Freedman S.B., Folmer B., Goldbach E., Holsztynska E.J., Hu K.L., Johnson-Wood K.L., Kennedy S.L., Kholodenko D., Knops J.E., Latimer L.H., Lee M., Liao Z., Lieberburg I.M., Motter R.N., Mutter L.C., Nietz J., Quinn K.P., Sacchi K.L., Seubert P.A., Shopp G.M., Thorsett E.D., Tung J.S., Wu J., Yang S., Yin C.T., Schenk D.B., May P.C., Altstiel L.D., Bender M.H., Boggs L.N., Britton T.C., Clemens J.C., Czilli D.L., Dieckman-McGinty D.K., Droste J.J., Fuson K.S., Gitter B.D., Hyslop P.A., Johnstone E.M., Li W.Y., Little S.P., Mabry T.E., Miller F.D., Audia J.E. Functional gamma-secretase inhibitors reduce beta-amyloid peptide levels in brain. J. Neurochem. 2001, 76:173-181.
12. Vingtdeux V., Hamdane M., Gompel M., Bégard S., Drobecq H., Ghestem A., Grosjean M.E., Kostanjevecki V., Grognet P., Vanmechelen E., Buée L., Delacourte A., Sergeant N. Phosphorylation of amyloid precursor carboxy-terminal fragments enhances their processing by a gamma-secretase-dependent mechanism. Neurobiol. Dis. 2005, 20:625-637.
13. Nunan J., Shearman M.S., Checler F., Cappai R., Evin G., Beyreuther K., Masters C.L., Small D.H. The C-terminal fragment of the Alzheimer's disease amyloid protein precursor is degraded by a proteasome-dependent mechanism distinct from gamma-secretase. Eur. J. Biochem. 2001, 268:5329-5336.
14. Chico L.K., Van Eldik L.J., Watterson D.M. Targeting protein kinases in central nervous system disorders. Nat. Rev. Drug Discov. 2009, 8:892-909.
15. Namura S., Iihara K., Takami S., Nagata I., Kikuchi H., Matsushita K., Moskowitz M.A., Bonventre J.V., Alessandrini A. Intravenous administration of MEK inhibitor U0126 affords brain protection against forebrain ischemia and focal cerebral ischemia. Proc. Natl. Acad. Sci. USA 2001, 98:11569-11574.
16. Wang X., Wang H., Xu L., Rozanski D.J., Sugawara T., Chan P.H., Trzaskos J.M., Feuerstein G.Z. Significant neuroprotection against ischemic brain injury by inhibition of the MEK1 protein kinase in mice. exploration of potential mechanism associated with apoptosis. J. Pharmacol. Exp. Ther. 2003, 304:172-178.