Modulation of γ-secretase activity by multiple enzyme-substrate interactions: Implications in pathogenesis of alzheimer's disease

PLoS ONE

Volumn 7, Issue 3, 2012, Pages

  Svedružić, Željko M ^a   Popović, Katarina ^a   Smoljan, Ivana ^a   Šendula Jengić, Vesna ^a  

^a UNIVERSITY OF RIJEKA   (Croatia)

Author keywords

[No Author keywords available]

Indexed keywords

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

ALZHEIMER DISEASE; ANIMAL CELL; ARTICLE; CARBOXY TERMINAL SEQUENCE; CATALYSIS; CONCENTRATION RESPONSE; EMBRYO; ENZYME ACTIVATION; ENZYME ACTIVITY; ENZYME BINDING; ENZYME INHIBITION; ENZYME METABOLISM; ENZYME SUBSTRATE COMPLEX; HUMAN; HYDROPHOBICITY; MOLECULAR PATHOLOGY; MOUSE; MUTATION; NEUROPATHOLOGY; NONHUMAN; PROTEIN CLEAVAGE; PROTEIN DOMAIN; PROTEIN SECRETION; REGULATORY MECHANISM; STEADY STATE;

EID: 84880755807     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0032293     Document Type: Article

References (99)

1. Blennow K, de Leon MJ, Zetterberg H, (2006) Alzheimer's disease. Lancet 368: 387-403.
2. Thathiah A, De Strooper B, (2009) G protein-coupled receptors, cholinergic dysfunction, and Abeta toxicity in Alzheimer's disease. Sci Signal 2: re8.
3. Tomita T, (2009) Secretase inhibitors and modulators for Alzheimer's disease treatment. Expert Rev Neurother 9: 661-679.
4. Kreft AF, Martone R, Porte A, (2009) Recent advances in the identification of gamma-secretase inhibitors to clinically test the Abeta oligomer hypothesis of Alzheimer's disease. J Med Chem 52: 6169-6188.
5. Fan J, Donkin J, Wellington C, (2009) Greasing the wheels of Abeta clearance in Alzheimer's disease: the role of lipids and apolipoprotein E. Biofactors 35: 239-248.
6. Thathiah A, De Strooper B, (2011) The role of G protein-coupled receptors in the pathology of Alzheimer's disease. Nat Rev Neurosci 12: 73-87.
7. Mawuenyega KG, Sigurdson W, Ovod V, Munsell L, Kasten T, et al. (2010) Decreased clearance of CNS beta-amyloid in Alzheimer's disease. Science 330: 1774.
8. O'Brien RJ, Wong PC, (2011) Amyloid Precursor Protein Processing and Alzheimers Disease. Annu Rev Neurosci 34: 185-204.
9. Du H, Guo L, Yan S, Sosunov AA, McKhann GM, et al. (2010) Early deficits in synaptic mitochondria in an Alzheimer's disease mouse model. Proc Natl Acad Sci U S A 107: 18670-18675.
10. De Strooper B, Vassar R, Golde T, (2010) The secretases: enzymes with therapeutic potential in Alzheimer disease. Nat Rev Neurol 6: 99-107.
11. Erez E, Fass D, Bibi E, (2009) How intramembrane proteases bury hydrolytic reactions in the membrane. Nature 459: 371-378.
12. De Strooper B, Annaert W, (2010) Novel research horizons for presenilins and gamma-secretases in cell biology and disease. Annu Rev Cell Dev Biol 26: 235-260.
13. Fraering PC, (2007) Structural and Functional Determinants of gamma-Secretase, an Intramembrane Protease Implicated in Alzheimer's Disease. Curr Genomics 8: 531-549.
14. Wolfe MS, Xia W, Ostaszewski BL, Diehl TS, Kimberly WT, et al. (1999) Two transmembrane aspartates in presenilin-1 required for presenilin endoproteolysis and gamma-secretase activity. Nature 398: 513-517.
15. Shearman MS, Beher D, Clarke EE, Lewis HD, Harrison T, et al. (2000) L-685,458, an aspartyl protease transition state mimic, is a potent inhibitor of amyloid beta-protein precursor gamma-secretase activity. Biochemistry 39: 8698-8704.
16. Perez-Revuelta BI, Fukumori A, Lammich S, Yamasaki A, Haass C, et al. (2010) Requirement for small side chain residues within the GxGD-motif of presenilin for gamma-secretase substrate cleavage. J Neurochem 112: 940-950.
17. Li YM, Lai MT, Xu M, Huang Q, DiMuzio-Mower J, et al. (2000) Presenilin 1 is linked with gamma-secretase activity in the detergent solubilized state. Proc Natl Acad Sci U S A 97: 6138-6143.
18. Tolia A, Chavez-Gutierrez L, De Strooper B, (2006) Contribution of presenilin transmembrane domains 6 and 7 to a water-containing cavity in the gamma-secretase complex. J Biol Chem 281: 27633-27642.
19. Lazarov VK, Fraering PC, Ye W, Wolfe MS, Selkoe DJ, et al. (2006) Electron microscopic structure of purified, active gamma-secretase reveals an aqueous intramembrane chamber and two pores. Proc Natl Acad Sci U S A 103: 6889-6894.
20. De Strooper B, (2007) Loss-of-function presenilin mutations in Alzheimer disease. Talking Point on the role of presenilin mutations in Alzheimer disease. EMBO Rep 8: 141-146.
21. Imbimbo BP, Panza F, Frisardi V, Solfrizzi V, D'Onofrio G, et al. (2010) Therapeutic intervention for Alzheimer's disease with gamma-secretase inhibitors: still a viable option? Expert Opin Investig Drugs 20: 325-341.
22. Serneels L, Van Biervliet J, Craessaerts K, Dejaegere T, Horre K, et al. (2009) gamma-Secretase heterogeneity in the Aph1 subunit: relevance for Alzheimer's disease. Science 324: 639-642.
23. Fukumoto H, Rosene DL, Moss MB, Raju S, Hyman BT, et al. (2004) Beta-secretase activity increases with aging in human, monkey, and mouse brain. Am J Pathol 164: 719-725.
24. Holsinger RM, McLean CA, Collins SJ, Masters CL, Evin G, (2004) Increased beta-Secretase activity in cerebrospinal fluid of Alzheimer's disease subjects. Ann Neurol 55: 898-899.
25. Li R, Lindholm K, Yang LB, Yue X, Citron M, et al. (2004) Amyloid beta peptide load is correlated with increased beta-secretase activity in sporadic Alzheimer's disease patients. Proc Natl Acad Sci U S A 101: 3632-3637.
26. Sun A, Koelsch G, Tang J, Bing G, (2002) Localization of beta-secretase memapsin 2 in the brain of Alzheimer's patients and normal aged controls. Exp Neurol 175: 10-22.
27. Yang LB, Lindholm K, Yan R, Citron M, Xia W, et al. (2003) Elevated beta-secretase expression and enzymatic activity detected in sporadic Alzheimer disease. Nat Med 9: 3-4.
28. Guyant-Marechal L, Rovelet-Lecrux A, Goumidi L, Cousin E, Hannequin D, et al. (2007) Variations in the APP gene promoter region and risk of Alzheimer disease. Neurology 68: 684-687.
29. Rovelet-Lecrux A, Frebourg T, Tuominen H, Majamaa K, Campion D, et al. (2007) APP locus duplication in a Finnish family with dementia and intracerebral haemorrhage. J Neurol Neurosurg Psychiatry 78: 1158-1159.
30. Rovelet-Lecrux A, Hannequin D, Raux G, Le Meur N, Laquerriere A, et al. (2006) APP locus duplication causes autosomal dominant early-onset Alzheimer disease with cerebral amyloid angiopathy. Nat Genet 38: 24-26.
31. Citron M, Oltersdorf T, Haass C, McConlogue L, Hung AY, et al. (1992) Mutation of the beta-amyloid precursor protein in familial Alzheimer's disease increases beta-protein production. Nature 360: 672-674.
32. Cai XD, Golde TE, Younkin SG, (1993) Release of excess amyloid beta protein from a mutant amyloid beta protein precursor. Science 259: 514-516.
33. German DC, Eisch AJ, (2004) Mouse models of Alzheimer's disease: insight into treatment. Rev Neurosci 15: 353-369.
34. Marlow L, Canet RM, Haugabook SJ, Hardy JA, Lahiri DK, et al. (2003) APH1, PEN2, and Nicastrin increase Abeta levels and gamma-secretase activity. Biochem Biophys Res Commun 305: 502-509.
35. Refolo LM, Eckman C, Prada CM, Yager D, Sambamurti K, et al. (1999) Antisense-induced reduction of presenilin 1 expression selectively increases the production of amyloid beta42 in transfected cells. J Neurochem 73: 2383-2388.
36. Sambamurti K, Greig NH, Utsuki T, Barnwell EL, Sharma E, et al. (2011) Targets for AD treatment: conflicting messages from gamma-secretase inhibitors. J Neurochem 117: 359-374.
37. Kakuda N, Funamoto S, Yagishita S, Takami M, Osawa S, et al. (2006) Equimolar production of amyloid beta-protein and amyloid precursor protein intracellular domain from beta-carboxyl-terminal fragment by gamma-secretase. J Biol Chem 281: 14776-14786.
38. Yin YI, Bassit B, Zhu L, Yang X, Wang C, et al. (2007) {gamma}-Secretase Substrate Concentration Modulates the Abeta42/Abeta40 Ratio: implications for Alzheimer's disease. J Biol Chem 282: 23639-23644.
39. Burton CR, Meredith JE, Barten DM, Goldstein ME, Krause CM, et al. (2008) The amyloid-beta rise and gamma-secretase inhibitor potency depend on the level of substrate expression. J Biol Chem 283: 22992-23003.
40. Yagishita S, Morishima-Kawashima M, Tanimura Y, Ishiura S, Ihara Y, (2006) DAPT-induced intracellular accumulations of longer amyloid beta-proteins: further implications for the mechanism of intramembrane cleavage by gamma-secretase. Biochemistry 45: 3952-3960.
41. Lanz TA, Karmilowicz MJ, Wood KM, Pozdnyakov N, Du P, et al. (2006) Concentration-dependent modulation of amyloid-beta in vivo and in vitro using the gamma-secretase inhibitor, LY-450139. J Pharmacol Exp Ther 319: 924-933.
42. Beel AJ, Mobley CK, Kim HJ, Tian F, Hadziselimovic A, et al. (2008) Structural studies of the transmembrane C-terminal domain of the amyloid precursor protein (APP): does APP function as a cholesterol sensor? Biochemistry 47: 9428-9446.
43. Gorman PM, Kim S, Guo M, Melnyk RA, McLaurin J, et al. (2008) Dimerization of the transmembrane domain of amyloid precursor proteins and familial Alzheimer's disease mutants. BMC Neurosci 9: 17.
44. Kienlen-Campard P, Tasiaux B, Van Hees J, Li M, Huysseune S, et al. (2008) Amyloidogenic processing but not amyloid precursor protein (APP) intracellular C-terminal domain production requires a precisely oriented APP dimer assembled by transmembrane GXXXG motifs. J Biol Chem 283: 7733-7744.
45. Munter LM, Voigt P, Harmeier A, Kaden D, Gottschalk KE, et al. (2007) GxxxG motifs within the amyloid precursor protein transmembrane sequence are critical for the etiology of Abeta42. Embo J 26: 1702-1712.
46. Eggert S, Midthune B, Cottrell B, Koo EH, (2009) Induced dimerization of the amyloid precursor protein leads to decreased amyloid-beta protein production. J Biol Chem 284: 28943-28952.
47. Wang H, Barreyro L, Provasi D, Djemil I, Torres-Arancivia C, et al. (2011) Molecular determinants and thermodynamics of the amyloid precursor protein transmembrane domain implicated in Alzheimer's disease. J Mol Biol 408: 879-895.
48. Takami M, Nagashima Y, Sano Y, Ishihara S, Morishima-Kawashima M, et al. (2009) gamma-Secretase: successive tripeptide and tetrapeptide release from the transmembrane domain of beta-carboxyl terminal fragment. J Neurosci 29: 13042-13052.
49. Yagishita S, Morishima-Kawashima M, Ishiura S, Ihara Y, (2008) Abeta46 is processed to Abeta40 and Abeta43, but not to Abeta42, in the low density membrane domains. J Biol Chem 283: 733-738.
50. Qi-Takahara Y, Morishima-Kawashima M, Tanimura Y, Dolios G, Hirotani N, et al. (2005) Longer forms of amyloid beta protein: implications for the mechanism of intramembrane cleavage by gamma-secretase. J Neurosci 25: 436-445.
51. Hebda JA, Miranker AD, (2009) The interplay of catalysis and toxicity by amyloid intermediates on lipid bilayers: insights from type II diabetes. Annu Rev Biophys 38: 125-152.
52. Kirkitadze MD, Condron MM, Teplow DB, (2001) Identification and characterization of key kinetic intermediates in amyloid beta-protein fibrillogenesis. J Mol Biol 312: 1103-1119.
53. Ono K, Condron MM, Teplow DB, (2009) Structure-neurotoxicity relationships of amyloid beta-protein oligomers. Proc Natl Acad Sci U S A 106: 14745-14750.
54. Bitan G, Kirkitadze MD, Lomakin A, Vollers SS, Benedek GB, et al. (2003) Amyloid beta-protein (Abeta) assembly: Abeta 40 and Abeta 42 oligomerize through distinct pathways. Proc Natl Acad Sci U S A 100: 330-335.
55. Peralvarez-Marin A, Mateos L, Zhang C, Singh S, Cedazo-Minguez A, et al. (2009) Influence of residue 22 on the folding, aggregation profile, and toxicity of the Alzheimer's amyloid beta peptide. Biophys J 97: 277-285.
56. Kuperstein I, Broersen K, Benilova I, Rozenski J, Jonckheere W, et al. (2010) Neurotoxicity of Alzheimer's disease Abeta peptides is induced by small changes in the Abeta42 to Abeta40 ratio. Embo J 29: 3408-3420.
57. Miyashita N, Straub JE, Thirumalai D, Sugita Y, (2009) Transmembrane structures of amyloid precursor protein dimer predicted by replica-exchange molecular dynamics simulations. J Am Chem Soc 131: 3438-3439.
58. Sato T, Tang TC, Reubins G, Fei JZ, Fujimoto T, et al. (2009) 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 106: 1421-1426.
59. Saito T, Suemoto T, Brouwers N, Sleegers K, Funamoto S, et al. (2011) Potent amyloidogenicity and pathogenicity of Abeta43. Nat Neurosci 14: 1023-1032.
60. Da Costa Dias B, Jovanovic K, Gonsalves D, Weiss SF, (2011) Structural and mechanistic commonalities of amyloid-beta and the prion protein. Prion 5: 126-137.
61. Benilova I, De Strooper B, (2011) An overlooked neurotoxic species in Alzheimer's disease. Nat Neurosci 14: 949-950.
62. Fersht A, (1998) Structure and Mechanism in Protein Science: A Guide to Enzyme Catalysis and Protein Folding (Hardcover): W. H. Freeman; 1st edition.
63. Tipton KF, eds. (2002) Enzyme Assays. 2nd Edition ed Oxford University Press pp. 282 p.
64. Svedruzic ZM, Reich NO, (2005) Mechanism of allosteric regulation of Dnmt1's processivity. Biochem 44: 14977-14988.
65. Fraering PC, Ye W, Strub JM, Dolios G, LaVoie MJ, et al. (2004) Purification and characterization of the human gamma-secretase complex. Biochemistry 43: 9774-9789.
66. Tian G, Sobotka-Briner CD, Zysk J, Liu X, Birr C, et al. (2002) Linear non-competitive inhibition of solubilized human gamma-secretase by pepstatin A methylester, L685458, sulfonamides, and benzodiazepines. J Biol Chem 277: 31499-31505.
67. Comery TA, Martone RL, Aschmies S, Atchison KP, Diamantidis G, et al. (2005) Acute gamma-secretase inhibition improves contextual fear conditioning in the Tg2576 mouse model of Alzheimer's disease. J Neurosci 25: 8898-8902.
68. Basi GS, Hemphill S, Brigham EF, Liao A, Aubele DL, et al. (2010) Amyloid precursor protein selective gamma-secretase inhibitors for treatment of Alzheimer's disease. Alzheimers Res Ther 2: 36.
69. Motulsky H, Christopoulos A, (2004) Fitting Models to Biological Data Using Linear and Nonlinear Regression: A Practical Guide to Curve Fitting Oxford University Press, USA; 1 edition pp. 352 p.
70. Tian G, Ghanekar SV, Aharony D, Shenvi AB, Jacobs RT, et al. (2003) The mechanism of gamma-secretase: multiple inhibitor binding sites for transition state analogs and small molecule inhibitors. J Biol Chem 278: 28968-28975.
71. Morohashi Y, Kan T, Tominari Y, Fuwa H, Okamura Y, et al. (2006) C-terminal fragment of presenilin is the molecular target of a dipeptidic gamma-secretase-specific inhibitor DAPT (N-[N-(3,5-difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester). J Biol Chem 281: 14670-14676.
72. Uemura K, Farner KC, Hashimoto T, Nasser-Ghodsi N, Wolfe MS, et al. (2010) Substrate docking to gamma-secretase allows access of gamma-secretase modulators to an allosteric site. Nat Commun 1: 130.
73. Uemura K, Lill CM, Li X, Peters JA, Ivanov A, et al. (2009) Allosteric modulation of PS1/gamma-secretase conformation correlates with amyloid beta(42/40) ratio. PLoS One 4: e7893.
74. Srivastava DK, Bernhard SA, (1987) Biophysical chemistry of metabolic reaction sequences in concentrated enzyme solution and in the cell. Annu Rev Biophys Biophys Chem 16: 175-204.
75. Van Noorden CJ, Jonges GN, (1995) Analysis of enzyme reactions in situ. Histochem J 27: 101-118.
76. Harris GC, Königer C, (1997) The 'high' concentrations of enzymes within the chloroplast Photosynthesis Research 54: 5-23.
77. Rushworth JV, Hooper NM, (2011) Lipid Rafts: Linking Alzheimer's Amyloid-beta Production, Aggregation, and Toxicity at Neuronal Membranes. Int J Alzheimers Dis 2011 1-14 pp. 1-14.
78. Tabaton M, Tamagno E, (2007) The molecular link between beta- and gamma-secretase activity on the amyloid beta precursor protein. Cell Mol Life Sci 64: 2211-2218.
79. Minton AP, (2000) Implications of macromolecular crowding for protein assembly. Curr Opin Struct Biol 10: 34-39.
80. Zimmerman SB, Minton AP, (1993) Macromoleculare Crowding: Biochemical, Biophysical, and Physiological Consequences. Annual Review of Biophysic and Biomolecular Structure 22: 27-65.
81. Beel AJ, Sanders CR, (2008) Substrate specificity of gamma-secretase and other intramembrane proteases. Cell Mol Life Sci 65: 1311-1334.
82. Gralle M, Botelho MG, Wouters FS, (2009) Neuroprotective secreted amyloid precursor protein acts by disrupting amyloid precursor protein dimers. J Biol Chem 284: 15016-15025.
83. Asada-Utsugi M, Uemura K, Noda Y, Kuzuya A, Maesako M, et al. (2011) N-cadherin enhances APP dimerization at the extracellular domain and modulates Abeta production. J Neurochem 119: 354-363.
84. Kwok JB, Taddei K, Hallupp M, Fisher C, Brooks WS, et al. (1997) Two novel (M233T and R278T) presenilin-1 mutations in early-onset Alzheimer's disease pedigrees and preliminary evidence for association of presenilin-1 mutations with a novel phenotype. Neuroreport 8: 1537-1542.
85. Bentahir M, Nyabi O, Verhamme J, Tolia A, Horre K, et al. (2006) Presenilin clinical mutations can affect gamma-secretase activity by different mechanisms. J Neurochem 96: 732-742.
86. Henley DB, May PC, Dean RA, Siemers ER, (2009) Development of semagacestat (LY450139), a functional gamma-secretase inhibitor, for the treatment of Alzheimer's disease. Expert Opin Pharmacother 10: 1657-1664.
87. Johnson-Wood K, Lee M, Motter R, Hu K, Gordon G, et al. (1997) Amyloid precursor protein processing and A beta42 deposition in a transgenic mouse model of Alzheimer disease. Proc Natl Acad Sci U S A 94: 1550-1555.
88. Citron M, Diehl TS, Gordon G, Biere AL, Seubert P, et al. (1996) Evidence that the 42- and 40-amino acid forms of amyloid beta protein are generated from the beta-amyloid precursor protein by different protease activities. Proc Natl Acad Sci U S A 93: 13170-13175.
89. Chavez-Gutierrez L, Tolia A, Maes E, Li T, Wong PC, et al. (2008) Glu(332) in the Nicastrin ectodomain is essential for gamma-secretase complex maturation but not for its activity. J Biol Chem 283: 20096-20105.
90. Chen AC, Guo LY, Ostaszewski BL, Selkoe DJ, Lavoie MJ, (2010) APH-1 associates directly with full-length and C-terminal fragments of gamma-secretase substrates. J Biol Chem 285: 11378-11391.
91. Szekeres PG, Leong K, Day TA, Kingston AE, Karran EH, (2008) Development of homogeneous 384-well high-throughput screening assays for Abeta1-40 and Abeta1-42 using AlphaScreen technology. J Biomol Screen 13: 101-111.
92. Wiltfang J, Esselmann H, Bibl M, Smirnov A, Otto M, et al. (2002) Highly conserved and disease-specific patterns of carboxyterminally truncated Abeta peptides 1-37/38/39 in addition to 1-40/42 in Alzheimer's disease and in patients with chronic neuroinflammation. J Neurochem 81: 481-496.
93. He G, Luo W, Li P, Remmers C, Netzer WJ, et al. (2010) Gamma-secretase activating protein is a therapeutic target for Alzheimer's disease. Nature 467: 95-98.
94. Lauren J, Gimbel DA, Nygaard HB, Gilbert JW, Strittmatter SM, (2009) Cellular prion protein mediates impairment of synaptic plasticity by amyloid-beta oligomers. Nature 457: 1128-1132.
95. Hulko M, Lupas AN, Martin J, (2007) Inherent chaperone-like activity of aspartic proteases reveals a distant evolutionary relation to double-psi barrel domains of AAA-ATPases. Protein Sci 16: 644-653.
96. Lemberg MK, Freeman M, (2007) Functional and evolutionary implications of enhanced genomic analysis of rhomboid intramembrane proteases. Genome Res 17: 1634-1646.
97. Nelson O, Tu H, Lei T, Bentahir M, de Strooper B, et al. (2007) Familial Alzheimer disease-linked mutations specifically disrupt Ca2+ leak function of presenilin 1. J Clin Invest 117: 1230-1239.
98. Barshop BA, Wrenn RF, Frieden C, (1983) Analysis of numerical methods for computer simulation of kinetic processes: development of KINSIM--a flexible, portable system. Anal Biochem 130: 134-145.
99. Mendes P, (1997) Biochemistry by numbers: simulation of biochemical pathways with Gepasi 3. Trends Biochem Sci 22: 361-363.