Are γ-secretase and its associated Alzheimer's disease γ problems?

Medical Hypotheses

Volumn 78, Issue 2, 2012, Pages 299-304

  Rodríguez Manotas, Miguel ^a   Amorín Díaz, Manuel ^b   Cabezas Herrera, Juan ^c   Acedo Martínez, Antonio ^a   Llorca Escuín, Ismael ^a  

^a HOSPITAL VEGA BAJA   (Spain)

^b HOSPITAL DE JOVE   (Spain)

^c HOSPITAL UNIVERSITARIO VIRGEN DE LA ARRIXACA   (Spain)

Author keywords

[No Author keywords available]

Indexed keywords

AMYLOID BETA PROTEIN[1-40]; AMYLOID BETA PROTEIN[1-42]; AMYLOID BETA PROTEIN[25-35]; AMYLOID PRECURSOR PROTEIN; GAMMA SECRETASE; PRESENILIN;

ALZHEIMER DISEASE; AMINO ACID SEQUENCE; ARTICLE; DOWN SYNDROME; HUMAN; KINETICS; PROTEIN DEGRADATION; PROTEIN FUNCTION;

ALZHEIMER DISEASE; AMYLOID BETA-PEPTIDES; AMYLOID PRECURSOR PROTEIN SECRETASES; HUMANS; MEMORY; MODELS, BIOLOGICAL; PEPTIDE FRAGMENTS; PRESENILIN-1; PRESENILIN-2; PROTEIN BINDING; SUBSTRATE SPECIFICITY;

EID: 84855188381     PISSN: 03069877     EISSN: 15322777     Source Type: Journal    
DOI: 10.1016/j.mehy.2011.11.007     Document Type: Article

References (37)

1. Lleo A., Blesa R., Queralt R., Ezquerra M., Molinuevo J.L., Pena-Casanova J., et al. Frequency of mutations in the presenilin and amyloid precursor protein genes in early-onset Alzheimer disease in Spain. Arch. Neurol. 2002, 59:1759-1763.
2. De Strooper B. Aph-1, Pen-2, and Nicastrin with Presenilin generate an active gamma-Secretase complex. Neuron 2003, 38:9-12.
3. De Strooper B., Annaert W., Cupers P., Saftig P., Craessaerts K., Mumm J.S., et al. A presenilin-1-dependent gamma-secretase-like protease mediates release of Notch intracellular domain. Nature 1999, 398:518-522.
4. Artavanis-Tsakonas S., Matsuno K., Fortini M.E. Notch signaling. Science 1995, 268:225-232.
5. Struhl G., Greenwald I. Presenilin is required for activity and nuclear access of Notch in Drosophila. Nature 1999, 398:522-525.
6. Bergmans B.A., De Strooper B. Gamma-secretases: from cell biology to therapeutic strategies. Lancet Neurol. 2010, 9:215-226.
7. Berezovska O., Jack C., Deng A., Gastineau N., Rebeck G.W., Hyman B.T. Notch1 and amyloid precursor protein are competitive substrates for presenilin1-dependent gamma-secretase cleavage. J. Biol. Chem. 2001, 276:30018-30023.
8. Lleo A., Berezovska O., Ramdya P., Fukumoto H., Raju S., Shah T., et al. Notch1 competes with the amyloid precursor protein for gamma-secretase and down-regulates presenilin-1 gene expression. J. Biol. Chem. 2003, 278:47370-47375.
9. Fischer D.F., Van D.R., Sluijs J.A., Nair S.M., Racchi M., Levelt C.N., et al. Ac of the Notch pathway in Down syndrome: cross-talk of Notch and APP. FASEB J. 2005, 19:1451-1458.
10. Takami M., Nagashima Y., Sano Y., Ishihara S., Morishima-Kawashima M., Funamoto S., et al. Gamma-Secretase: successive tripeptide and tetrapeptide release from the transmembrane domain of beta-carboxyl terminal fragment. J. Neurosci. 2009, 29:13042-13052.
11. Qi-Takahara Y., Morishima-Kawashima M., Tanimura Y., Dolios G., Hirotani N., Horikoshi Y., et al. Longer forms of amyloid beta protein: implications for the mechanism of intramembrane cleavage by gamma-ecretase. J. Neurosci. 2005, 25:436-445.
12. Osenkowski P., Li H., Ye W., Li D., Aeschbach L., Fraering P.C., et al. Cryoelectron microscopy structure of purified gamma-secretase at 12 A resolution. J. Mol. Biol. 2009, 385:642-652.
13. Urban S., Shi Y. Core principles of intramembrane proteolysis: comparison of rhomboid and site-2 family proteases. Curr. Opin. Struct. Biol. 2008, 18:432-441.
14. Kakuda N., Funamoto S., Yagishita S., Takami M., Osawa S., Dohmae N., et al. Equimolar production of amyloid beta-protein and amyloid precursor protein intracellular domain from beta-carboxyl-terminal fragment by gamma-secretase. J. Biol. Chem. 2006, 281:14776-14786.
15. Yu H., Saura C.A., Choi S.Y., Sun L.D., Yang X., Handler M., et al. APP processing and synaptic plasticity in presenilin-1 conditional knockout mice. Neuron 2001, 31:713-726.
16. Zhou L., Brouwers N., Benilova I., Vandersteen A., Mercken M., Van L.K., et al. Amyloid precursor protein mutation E682K at the alternative beta-secretase cleavage beta'-site increases Abeta generation. EMBO Mol. Med. 2011, 3:291-302.
17. Busciglio J., Pelsman A., Wong C., Pigino G., Yuan M., Mori H., et al. Altered metabolism of the amyloid beta precursor protein is associated with mitochondrial dysfunction in Down's syndrome. Neuron 2002, 33:677-688.
18. Hebert S.S., Bourdages V., Godin C., Ferland M., Carreau M., Levesque G. Presenilin-1 interacts directly with the beta-site amyloid protein precursor cleaving enzyme (BACE1). Neurobiol. Dis. 2003, 13:238-245.
19. Renzi F., Zhang X., Rice W.J., Torres-Arancivia C., Gomez-Llorente Y., Diaz R., et al. Structure of {gamma}-Secretase and Its Trimeric Pre-activation Intermediate by Single-particle Electron Microscopy. J. Biol. Chem. 2011, 286:21440-21449.
20. Qahwash I., He W., Tomasselli A., Kletzien R.F., Yan R. Processing amyloid precursor protein at the beta-site requires proper orientation to be accessed by BACE1. J. Biol. Chem. 2004, 279:39010-39016.
21. Sun X., Tong Y., Qing H., Chen C.H., Song W. Increased BACE1 maturation contributes to the pathogenesis of Alzheimer's disease in Down syndrome. FASEB J. 2006, 20:1361-1368.
22. Sato T., Tang T.C., Reubins G., Fei J.Z., Fujimoto T., Kienlen-Campard P., et al. A helix-to-coil transition at the epsilon-cut site in the transmembrane dimer of the amyloid precursor protein is required for proteolysis. Proc. Natl. Acad. Sci. U.S.A. 2009, 106:1421-1426.
23. Funamoto S., Morishima-Kawashima M., Tanimura Y., Hirotani N., Saido T.C., Ihara Y. Truncated carboxyl-terminal fragments of beta-amyloid precursor protein are processed to amyloid beta-proteins 40 and 42. Biochemistry 2004, 43:13532-13540.
24. Yagishita S., Morishima-Kawashima M., Ishiura S., Ihara Y. Abeta46 is processed to Abeta40 and Abeta43, but not to Abeta42, in the low density membrane domains. J. Biol. Chem. 2008, 283:733-738.
25. Li H., Wolfe M.S., Selkoe D.J. Toward structural elucidation of the gamma-secretase complex. Structure 2009, 17:326-334.
26. Sato T., Dohmae N., Qi Y., Kakuda N., Misonou H., Mitsumori R., et al. Potential link between amyloid beta-protein 42 and C-terminal fragment gamma 49-99 of beta-amyloid precursor protein. J. Biol. Chem. 2003, 278:24294-24301.
27. Shen J., Kelleher R.J. The presenilin hypothesis of Alzheimer's disease: evidence for a loss-of-function pathogenic mechanism. Proc. Natl. Acad. Sci. U.S.A. 2007, 104:403-409.
28. Uemura K., Farner K.C., Hashimoto T., Nasser-Ghodsi N., Wolfe M.S., Koo E.H., et al. Substrate docking to gamma-secretase allows access of gamma-secretase modulators to an allosteric site. Nat. Commun. 2010, 1:130.
29. Lee E.B., Zhang B., Liu K., Greenbaum E.A., Doms R.W., Trojanowski J.Q., et al. BACE overexpression alters the subcellular processing of APP and inhibits Abeta deposition in vivo. J. Cell Biol. 2005, 168:291-302.
30. Pitsi D., Octave J.N. Presenilin 1 stabilizes the C-terminal fragment of the amyloid precursor protein independently of gamma-secretase activity. J. Biol. Chem. 2004, 279:25333-25338.
31. Bero A.W., Yan P., Roh J.H., Cirrito J.R., Stewart F.R., Raichle M.E., et al. Neuronal activity regulates the regional vulnerability to amyloid-beta deposition. Nat. Neurosci. 2011, 14:750-756.
32. Berger-Sweeney J., McPhie D.L., Arters J.A., Greenan J., Oster-Granite M.L., Neve R.L. Impairments in learning and memory accompanied by neurodegeneration in mice transgenic for the carboxyl-terminus of the amyloid precursor protein. Brain Res. Mol. Brain Res. 1999, 66:150-162.
33. Puzzo D., Privitera L., Leznik E., Fa M., Staniszewski A., Palmeri A., et al. Picomolar amyloid-beta positively modulates synaptic plasticity and memory in hippocampus. J. Neurosci. 2008, 28:14537-14545.
34. Hebert S.S., Serneels L., Tolia A., Craessaerts K., Derks C., Filippov M.A., et al. Regulated intramembrane proteolysis of amyloid precursor protein and regulation of expression of putative target genes. EMBO Rep. 2006, 7:739-745.
35. De Strooper B., Annaert W. Novel research horizons for presenilins and gamma-secretases in cell biology and disease. Annu. Rev. Cell Dev. Biol. 2010, 26:235-260.
36. Wikipedia, the free encyclopedia, Flip-flop (electronics), Last updated August 14, 2011, Accessed on July 10, 2011. http://en.wikipedia.org/wiki/Flip-flop_(electronics).
37. Alberi L., Liu S., Wang Y., Badie R., Smith-Hicks C., Wu J., et al. Activity-induced Notch signaling in neurons requires Arc/Arg3.1 and is essential for synaptic plasticity in hippocampal networks. Neuron 2011, 69:437-444.