Presenilin/γ-secretase and inflammation

Frontiers in Aging Neuroscience

Volumn 2, Issue MAY, 2010, Pages

  Saura, Carlos A ^a  

^a UNIVERSITAT AUTÒNOMA DE BARCELONA   (Spain)

Author keywords

Alzheimer's disease; Amyloid; Frontotemporal dementia; Neurodegeneration; Neuroinflammation; Notch; NSAID

Indexed keywords

EID: 79551484106     PISSN: None     EISSN: 16634365     Source Type: Journal    
DOI: 10.3389/fnagi.2010.00016     Document Type: Review

References (111)

1. Agdeppa, E. D., Kepe, V., Petri, A., Satyamurthy, N., Liu, J., Huang, S. C., Small, G. W., Cole, G. M., and Barrio, J. R. (2003). In vitro detection of (S)-naproxen and ibuprofen binding to plaques in the Alzheimer's brain using the positron emission tomography molecular imaging probe 2-(1-[6-[(2-[(18)F]fluoroethyl)(methyl)amino]-2-naphthyl]ethylidene) malono nitrile. Neuroscience 117, 723-730.
2. Allan, S. M., and Rothwell, N. J. (2003). Inflammation in central nervous system injury. Philos. Trans. R. Soc. Lond., B, Biol. Sci. 358, 1669-1677.
3. Arumugam, T. V., Chan, S. L., Jo, D. G., Yilmaz, G., Tang, S. C., Cheng, A., Gleichmann, M., Okun, E., Dixit, V. D., Chigurupati, S., Mughal, M. R., Ouyang, X., Miele, L., Magnus, T., Poosala, S., Granger, D. N., and Mattson, M. P. (2006). Gamma secretase-mediated Notch signaling worsens brain damage and functional outcome in ischemic stroke. Nat. Med. 12, 621-623.
4. Bamberger, M. E., Harris, M. E., McDonald, D. R., Husemann, J., and Landreth, G. E. (2003). A cell surface receptor complex for fibrillar β-amyloid mediates microglial activation. J. Neurosci. 23, 2665-2674.
5. Bates, K. A., Fonte, J., Robertson, T. A., Martins, R. N., and Harvey, A. R. (2002). Chronic gliosis triggers Alzheimer's disease-like processing of amyloid precursor protein. Neuroscience 113, 785-796.
6. Beglopoulos, V., Sun, X., Saura, C. A., Lemere, C. A., Kim, R. D., and Shen, J. (2004). Reduced β-amyloid production and increased inflammatory responses in presenilin conditional knock-out mice. J. Biol. Chem. 279, 46907-46914.
7. Bernardi, L., Tomaino, C., Anfossi, M., Gallo, M., Geracitano, S., Costanzo, A., Colao, R., Puccio, G., Frangipane, F., Curcio, S. A., Mirabelli, M., Smirne, N., Iapaolo, D., Maletta, R. G., and Bruni, A. C. (2009). Novel PSEN1 and PGRN mutations in early-onset familial frontotemporal dementia. Neurobiol. Aging 30, 1825-1833.
8. Cervantes, S., Saura, C. A., Pomares, E., Gonzalez-Duarte, R., and Marfany, G. (2004). Functional implications of the presenilin dimerization: reconstitution of γ-secretase activity by assembly of a catalytic site at the dimer interface of two catalytically inactive presenilins. J. Biol. Chem. 279, 36519-36529.
9. Choi, S. H., Veeraraghavalu, K., Lazarov, O., Marler, S., Ransohoff, R. M., Ramirez, J. M., and Sisodia, S. S. (2008). Non-cell-autonomous effects of presenilin 1 variants on enrichment-mediated hippocampal progenitor cell proliferation and differentiation. Neuron 59, 568-580.
10. Coma, M., Sereno, L., Da Rocha-Souto, B., Scotton, T. C., España, J., Sánchez, M. B., Rodríguez, M., Agulló, J., Guardia-Laguarta, C., Garcia-Alloza, M., Borreli, L. A., Clarimón, J., Lleó, A., Bacskai, B. J., Saura, C. A., Hyman, B., and Gómez-Isla, T. (2010). Triflusal reduces dense-core plaque load, associated axonal alterations and inflammatory changes, and rescues cognition in a transgenic mouse model of Alzheimer's disease. Neurobiol. Dis. (in press). [Epub ahead of print].
11. Czirr, E., Leuchtenberger, S., Dorner-Ciossek, C., Schneider, A., Jucker, M., Koo, E. H., Pietrzik, C. U., Baumann, K., and Weggen, S. (2007). Insensitivity to Aβ42-lowering nonsteroidal anti-inflammatory drugs and γ-secretase inhibitors is common among aggressive presenilin-1 mutations. J. Biol. Chem. 282, 24504-24513.
12. Dermaut, B., Kumar-Singh, S., Engelborghs, S., Theuns, J., Rademakers, R., Saerens, J., Pickut, B. A., Peeters, K., Van Den Broeck, M., Vennekens, K., Claes, S., Cruts, M., Cras, P., Martin, J. J., Van Broeckhoven, C., and De Deyn, P. P. (2004). A novel presenilin 1 mutation associated with Pick's disease but not β-amyloid plaques. Ann. Neurol. 55, 617-626.
13. De Strooper, B. (2003). Aph-1, pen-2, and nicastrin with presenilin generate an active γ-secretase complex. Neuron 38, 9-12.
14. 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.
15. De Strooper, B., Annaert, W., Cupers, P., Saftig, P., Craessaerts, K., Mumm, J. S., Schroeter, E. H., Schrijvers, V., Wolfe, M. S., Ray, W. J., Goate, A., and Kopan, R. (1999). A presenilin-1-dependent γ-secretase-like protease mediates release of Notch intracellular domain. Nature 398, 518-522.
16. De Strooper, B., Saftig, P., Craessaerts, K., Vanderstichele, H., Guhde, G., Annaert, W., Figura, K., and Leuven, F. (1998). Deficiency of presenilin-1 inhibits the normal cleavage of amyloid precursor protein. Nature 391, 387-390.
17. Dewachter, I., Reverse, D., Caluwaerts, N., Ris, L., Kuiperi, C., Van den Haute, C., Spittaels, K., Umans, L., Serneels, L., Thiry, E., Moechars, D., Mercken, M., Godaux, E., and Van Leuven, F. (2002). Neuronal deficiency of presenilin 1 inhibits amyloid plaque formation and corrects hippocampal long-term potentiation but not a cognitive defect of amyloid precursor protein [V717I] transgenic mice. J. Neurosci. 22, 3445-3453.
18. Dewachter, I., Ris, L., Croes, S., Borghgraef, P., Devijver, H., Voets, T., Nilius, B., Godaux, E., and Van Leuven, F. (2008). Modulation of synaptic plasticity and Tau phosphorylation by wild-type and mutant presenilin1. Neurobiol. Aging 29, 639-652.
19. Dong, S., Li, C., Wu, P., Tsien, J. Z., and Hu, Y. (2007). Environment enrichment rescues the neurodegenerative phenotypes in presenilins-deficient mice. Eur. J. Neurosci. 26, 101-112.
20. Dumanchin, C., Tournier, I., Martin, C., Didic, M., Belliard, S., Carlander, B., Rouhart, F., Duyckaerts, C., Pellissier, J. F., Latouche, J. B., Hannequin, D., Frebourg, T., Tosi, M., and Campion, D. (2006). Biological effects of four PSEN1 gene mutations causing Alzheimer disease with spastic paraparesis and cotton wool plaques. Hum. Mutat. 27, 1063.
21. Eckert, A., Schindowski, K., Leutner, S., Luckhaus, C., Touchet, N., Czech, C., and Muller, W. E. (2001). Alzheimer's disease-like alterations in peripheral cells from presenilin-1 transgenic mice. Neurobiol. Dis. 8, 331-342.
22. Eikelenboom, P., and Veerhuis, R. (1996). The role of complement and activated microglia in the pathogenesis of Alzheimer's disease. Neurobiol. Aging 17, 673-680.
23. Eriksen, J. L., Sagi, S. A., Smith, T. E., Weggen, S., Das, P., McLendon, D. C., Ozols, V. V., Jessing, K. W., Zavitz, K. H., Koo, E. H., and Golde, T. E. (2003). NSAIDs and enantiomers of flurbiprofen target γ-secretase and lower Aβ42 in vivo. J. Clin. Invest. 112, 440-449.
24. Gaiano, N., and Fishell, G. (2002). The role of notch in promoting glial and neural stem cell fates. Annu. Rev. Neurosci. 25, 471-490.
25. Gaiano, N., Nye, J., and Fishell, G. (2000). Radial glial identity is promoted by Notch1 signaling in the murine forebrain. Neuron 26, 395-404.
26. Gomez-Isla, T., Growdon, W. B., McNamara, M. J., Nochlin, D., Bird, T. D., Arango, J. C., Lopera, F., Kosik, K. S., Lantos, P. L., Cairns, N. J., and Hyman, B. T. (1999). The impact of different presenilin 1 and presenilin 2 mutations on amyloid deposition, neurofibrillary changes and neuronal loss in the familial Alzheimer's disease brain: evidence for other phenotype-modifying factors. Brain 122(Pt 9), 1709-1719.
27. Gomez-Tortosa, E., Barquero, S., Baron, M., Gil-Neciga, E., Castellanos, F., Zurdo, M., Manzano, S., Munoz, D. G., Jimenez-Huete, A., Rabano, A., Sainz, M. J., Guerrero, R., Gobernado, I., Perez-Perez, J., and Jimenez-Escrig, A. (2010). Clinical-genetic correlations in familial Alzheimer's disease caused by presenilin 1 mutations. J. Alzheimers Dis. 19, 873-884.
28. Green, R. C., Schneider, L. S., Amato, D. A., Beelen, A. P., Wilcock, G., Swabb, E. A., and Zavitz, K. H. (2009). Effect of tarenflurbil on cognitive decline and activities of daily living in patients with mild Alzheimer disease: a randomized controlled trial. JAMA 302, 2557-2564.
29. Gregory, G. C., Macdonald, V., Schofield, P. R., Kril, J. J., and Halliday, G. M. (2006). Differences in regional brain atrophy in genetic forms of Alzheimer's disease. Neurobiol. Aging 27, 387-393.
30. Handler, M., Yang, X., and Shen, J. (2000). Presenilin-1 regulates neuronal differentiation during neurogenesis. Development 127, 2593-2606.
31. Hardy, J., and Selkoe, D. (2002). The amyloid hypothesis of Alzheimer's disease: progress and problems on the road to therapeutics. Science 297, 353-356.
32. Heneka, M. T., Sastre, M., Dumitrescu-Ozimek, L., Hanke, A., Dewachter, I., Kuiperi, C., O'Banion, K., Klockgether, T., Van Leuven, F., and Landreth, G. E. (2005). Acute treatment with the PPARγ agonist pioglitazone and ibuprofen reduces glial inflammation and Aβ1-42 levels in APPV717I transgenic mice. Brain 128, 1442-1453.
33. Hirohata, M., Ono, K., Naiki, H., and Yamada, M. (2005). Non-steroidal anti-inflammatory drugs have anti-amyloidogenic effects for Alzheimer's β-amyloid fibrils in vitro. Neuropharmacology 49, 1088-1099.
34. Holmes, C., Cunningham, C., Zotova, E., Woolford, J., Dean, C., Kerr, S., Culliford, D., and Perry, V. H. (2009). Systemic inflammation and disease progression in Alzheimer disease. Neurology 73, 768-774.
35. Hutton, M. (2004). Presenilin mutations associated with fronto-temporal dementia. Ann. Neurol. 55, 604-606.
36. Ingelsson, M., Fukumoto, H., Newell, K. L., Growdon, J. H., Hedley-Whyte, E. T., Frosch, M. P., Albert, M. S., Hyman, B. T., and Irizarry, M. C. (2004). Early Aβ accumulation and progressive synaptic loss, gliosis, and tangle formation in AD brain. Neurology 62, 925-931.
37. in t' Veld, B. A., Ruitenberg, A., Hofman, A., Launer, L. J., van Duijn, C. M., Stijnen, T., Breteler, M. M., and Stricker, B. H. (2001). Nonsteroidal antiinflammatory drugs and the risk of Alzheimer's disease. N. Engl. J. Med. 345, 1515-1521.
38. Jack, C., Knopman, D., Jagust, W., Shaw, L., Aisen, P., Weiner, M., Petersen, R., and Tojanowski, J. (2010). Hypothetical model of dynamic biomarkers of the Alzheimer's pathological cascade. Lancet Neurol. 9, 119-128.
39. Jiang, X., Zhang, D., Shi, J., Chen, Y., Zhang, P., and Mei, B. (2009). Increased inflammatory response both in brain and in periphery in presenilins conditional double knock-out mice. J. Alzheimers Dis. 18, 515-523.
40. Johnston, J. M., Burnett, P., Thomas, A. P., and Tezapsidis, N. (2006). Calcium oscillations in type-1 astrocytes, the effect of a presenilin 1 (PS1) mutation. Neurosci. Lett. 395, 159-164.
41. Kim, K. S., Wegiel, J., Sapienza, V., Chen, J., Hong, H., and, Wisniewski, H. M. (1997). Immunoreactivity of presenilin-1 in human, rat and mouse brain. Brain Res. 757, 159-163.
42. Koo, E. H., and Kopan, R. (2004). Potential role of presenilin-regulated signaling pathways in sporadic neurodegeneration. Nat. Med. 10(Suppl.), S26-S33.
43. Kukar, T., Murphy, M. P., Eriksen, J. L., Sagi, S. A., Weggen, S., Smith, T. E., Ladd, T., Khan, M. A., Kache, R., Beard, J., Dodson, M., Merit, S., Ozols, V. V., Anastasiadis, P. Z., Das, P., Fauq, A., Koo, E. H., and Golde, T. E. (2005). Diverse compounds mimic Alzheimer disease-causing mutations by augmenting Aβ42 production. Nat. Med. 11, 545-550.
44. Kukar, T., Prescott, S., Eriksen, J. L., Holloway, V., Murphy, M. P., Koo, E. H., Golde, T. E., and Nicolle, M. M. (2007). Chronic administration of R-flurbiprofen attenuates learning impairments in transgenic amyloid precursor protein mice. BMC Neurosci. 8, 54.
45. Kukar, T. L., Ladd, T. B., Bann, M. A., Fraering, P. C., Narlawar, R., Maharvi, G. M., Healy, B., Chapman, R., Welzel, A. T., Price, R. W., Moore, B., Rangachari, V., Cusack, B., Eriksen, J., Jansen-West, K., Verbeeck, C., Yager, D., Eckman, C., Ye, W., Sagi, S., Cottrell, B. A., Torpey, J., Rosenberry, T. L., Fauq, A., Wolfe, M. S., Schmidt, B., Walsh, D. M., Koo, E. H., and Golde, T. E. (2008). Substrate-targeting γ-secretase modulators. Nature 453, 925-929.
46. Kumar-Singh, S., Theuns, J., Van Broeck, B., Pirici, D., Vennekens, K., Corsmit, E., Cruts, M., Dermaut, B., Wang, R., and Van Broeckhoven, C. (2006). Mean age-of-onset of familial Alzheimer disease caused by presenilin mutations correlates with both increased Aβ42 and decreased Aβ40. Hum. Mutat. 27, 686-695.
47. Lah, J. J., Heilman, C. J., Nash, N. R., Rees, H. D., Yi, H., Counts, S. E., and Levey, A. I. (1997). Light and electron microscopic localization of presenilin1 in primate brain. J. Neurosci. 17, 1971.
48. Laky, K., and Fowlkes, B. J. (2007). Presenilins regulate alphabeta T cell development by modulating TCR signaling. J. Exp. Med. 204, 2115-2129.
49. Laky, K., and Fowlkes, B. J. (2008). Notch signaling in CD4 and CD8 T cell development. Curr. Opin. Immunol. 20, 197-202.
50. Lathia, J. D., Mattson, M. P., and Cheng, A. (2008). Notch: from neural development to neurological disorders. J. Neurochem. 107, 1471-1481.
51. Le, T. V., Crook, R., Hardy, J., and Dickson, D. W. (2001). Cotton wool plaques in non-familial late-onset alzheimer disease. J. Neuropathol. Exp. Neurol. 60, 1051-1061.
52. Lee, M. K., Slunt, H. H., Martin, L. J., Thinakaran, G., Kim, G., Gandy, S. E., Seeger, M., Koo, E., Price, D. L., and Sisodia, S. S. (1996). Expression of presenilin 1 and 2 (PS1 and PS2) in human and murine tissues. J. Neurosci. 16, 7513-7525.
53. Lemere, C. A., Munger, J. S., Shi, G.-P., Natkin, L., Haass, C., Chapman, H. A., and Selkoe, D. J. (1995). The lysosomal cystein protease, cathepsin S, is increased in Alzheimer's disease and Down syndrome brain: an immunocytochemical study. Am. J. Pathol. 146, 848-860.
54. Levy-Lahad, E., Wasco, W., Poorkaj, P., Romano, D. M., Oshima, J., Pettingell, H., Yu, C., Jondro, P. D., Schmidt, S. D., Wang, K., Crowley, A. C., Fu, Y-H., Guenette, S. Y., Galas, D., Nemens, E., Wijsman, E. M., Bird, T. D., Schellenberg, G. D., and Tanzi, R. E. (1995). Candidate gene for the chromosome 1 familial Alzheimer's disease locus. Science 269, 973-977.
55. Lim, G. P., Yang, F., Chu, T., Chen, P., Beech, W., Teter, B., Tran, T., Ubeda, O., Ashe, K. H., Frautschy, S. A., and Cole, G. M. (2000). Ibuprofen suppresses plaque pathology and inflammation in a mouse model for Alzheimer's disease. J. Neurosci. 20, 5709-5714.
56. Lippa, C. F., Saunders, A. M., Smith, T. W., Swearer, J. M., Drachman, D. A., Ghetti, B., Nee, L., Pulaski-Salo, D., Dickson, D., Robitaille, Y., Bergeron, C., Crain, B., Benson, M. D., Farlow, M., Hyman, B. T., George-Hyslop, S. P., Roses, A. D., and Pollen, D. A. (1996). Familial and sporadic Alzheimer's disease: neuropathology cannot exclude a final common pathway. Neurology 46, 406-412.
57. Lleo, A., Berezovska, O., Herl, L., Raju, S., Deng, A., Bacskai, B. J., Frosch, M. P., Irizarry, M., and Hyman, B. T. (2004). Nonsteroidal anti-inflammatory drugs lower Aβ42 and change presenilin 1 conformation. Nat. Med. 10, 1065-1066.
58. Lynch, M. A. (2010). Age-related neuroinflammatory changes negatively impact on neuronal function. Front. Neurosci. 1, 1-8.
59. Mann, D. M., Takeuchi, A., Sato, S., Cairns, N. J., Lantos, P. L., Rossor, M. N., Haltia, M., Kalimo, H., and Iwatsubo, T. (2001). Cases of Alzheimer's disease due to deletion of exon 9 of the presenilin-1 gene show an unusual but characteristic β-amyloid pathology known as 'cotton wool' plaques. Neuropathol. Appl. Neurobiol. 27, 189-196.
60. Maraver, A., Tadokoro, C. E., Badura, M. L., Shen, J., Serrano, M., and Lafaille, J. J. (2007). Effect of presenilins in the apoptosis of thymocytes and homeostasis of CD8+ T cells. Blood 110, 3218-3225.
61. Martikainen, P., Pikkarainen, M., Pontynen, K., Hiltunen, M., Lehtovirta, M., Tuisku, S., Soininen, H., and Alafuzoff, I. (2009). Brain pathology in three subjects from the same pedigree with PSEN1 P264L mutation. Neuropathol. Appl. Neurobiol. 36, 41-54.
62. McGeer, P. L., and McGeer, E. G. (2007). NSAIDs and Alzheimer disease: epidemiological, animal model and clinical studies. Neurobiol. Aging 28, 639-647.
63. Moore, A. H., Wu, M., Shaftel, S. S., Graham, K. A., and O'Banion, M. K. (2009). Sustained expression of interleukin-1beta in mouse hippocampus impairs spatial memory. Neuroscience 164, 1484-1495.
64. Morgan, G. A., Guo, Q., Chan, S. L., Gary, D. S., Osborne, B. A., and Mattson, M. P. (2007). Defects of immune regulation in the presenilin-1 mutant knockin mouse. Neuromol. Med. 9, 35-45.
65. Mrak, R. E., and Griffin, W. S. (2005). Glia and their cytokines in progression of neurodegeneration. Neurobiol. Aging 26, 349-354.
66. Muller, T., Meyer, H. E., Egensperger, R., and Marcus, K. (2008). The amyloid precursor protein intracellular domain (AICD) as modulator of gene expression, apoptosis, and cytoskeletal dynamics-relevance for Alzheimer's disease. Prog. Neurobiol. 85, 393-406.
67. Munch, G., Gasic-Milenkovic, J., Dukic-Stefanovic, S., Kuhla, B., Heinrich, K., Riederer, P., Huttunen, H. J., Founds, H., and Sajithlal, G. (2003). Microglial activation induces cell death, inhibits neurite outgrowth and causes neurite retraction of differentiated neuroblastoma cells. Exp. Brain. Res. 150, 1-8.
68. Nadler, Y., Alexandrovich, A., Grigoriadis, N., Hartmann, T., Rao, K. S., Shohami, E., and Stein, R. (2008). Increased expression of the γ-secretase components presenilin-1 and nicastrin in activated astrocytes and microglia following traumatic brain injury. Glia 56, 552-567.
69. Nagele, R. G., D'Andrea, M. R., Lee, H., Venkataraman, V., and Wang, H. Y. (2003). Astrocytes accumulate Aβ42 and give rise to astrocytic amyloid plaques in Alzheimer disease brains. Brain Res. 971, 197-209.
70. Ni, C., Murphy, M., Golde, T., and Carpenter, G. (2001). γ-Secretase cleavage and nuclear localization of ErbB-4 receptor tyrosine kinase. Science 294, 2179-2181.
71. Nochlin, D., van Belle, G., Bird, T. D., and Sumi, S. M. (1993). Comparison of the severity of neuropathologic changes in familial and sporadic Alzheimer's disease. Alzheimer Dis. Assoc. Disord. 7, 212-222.
72. Ong, C. T., Sedy, J. R., Murphy, K. M., and Kopan, R. (2008). Notch and presenilin regulate cellular expansion and cytokine secretion but cannot instruct Th1/Th2 fate acquisition. PLoS ONE 3, e2823.
73. Page, R. M., Baumann, K., Tomioka, M., Perez-Revuelta, B. I., Fukumori, A., Jacobsen, H., Flohr, A., Luebbers, T., Ozmen, L., Steiner, H., and Haass, C. (2008). Generation of Aβ38 and Aβ42 is independently and differentially affected by familial Alzheimer disease-associated presenilin mutations and γ-secretase modulation. J. Biol. Chem. 283, 677-683.
74. Parachikova, A., Agadjanyan, M. G., Cribbs, D. H., Blurton-Jones, M., Perreau, V., Rogers, J., Beach, T. G., and Cotman, C. W. (2007). Inflammatory changes parallel the early stages of Alzheimer disease. Neurobiol. Aging 28, 1821-1833.
75. Peers, C., Dallas, M. L., Boycott, H. E., Scragg, J. L., Pearson, H. A., and Boyle, J. P. (2009). Hypoxia and neurodegeneration. Ann. N. Y. Acad. Sci. 1177, 169-177.
76. 2+ homeostasis in type I cortical astrocytes by hypoxia: evidence for association with Alzheimer's disease. Biol. Chem. 385, 285-289.
77. Raux, G., Gantier, R., Thomas-Anterion, C., Boulliat, J., Verpillat, P., Hannequin, D., Brice, A., Frebourg, T., and Campion, D. (2000). Dementia with prominent frontotemporal features associated with L113P presenilin 1 mutation. Neurology 55, 1577-1578.
78. Rocher-Ros, V., Marco, S., Mao, J. H., Gines, S., Metzger, D., Chambon, P., Balmain, A., and Saura, C. A. (2010). Presenilin modulates EGFR signaling and cell transformation by regulating the ubiquitin ligase Fbw7. Oncogene (in press). [Epub ahead of print]
79. Rogaev, E. I., Sherrington, R., Rogaeva, E. A., Levesque, G., Ikeda, M., Liang, Y., Chi, H., Lin, C., Holamn, K., Tsuda, T., Mar, L., Sorbi, S., Nacmias, B., Piacentini, S., Amaducci, L., Chumakov, I., Cohen, D., Lannfelt, L., Fraser, P. E., Rommens, J. M., and St. George-Hyslop, P. H. (1995). Familial Alzheimer's disease in kindreds with missense mutations in a gene on chromosome 1 related to the Alzheimer's disease type 3 gene. Nature 376, 775-778.
80. Sardi, S. P., Murtie, J., Koirala, S., Patten, B. A., and Corfas, G. (2006). Presenilin-dependent ErbB4 nuclear signaling regulates the timing of astrogenesis in the developing brain. Cell 127, 185-197.
81. Sastre, M., Dewachter, I., Rossner, S., Bogdanovic, N., Rosen, E., Borghgraef, P., Evert, B. O., Dumitrescu-Ozimek, L., Thal, D. R., Landreth, G., Walter, J., Klockgether, T., van Leuven, F., and Heneka, M. T. (2006). Nonsteroidal anti-inflammatory drugs repress β-secretase gene promoter activity by the activation of PPARgamma. Proc. Natl. Acad. Sci. U.S.A. 103, 443-448.
82. Saura, C. A., Chen, G., Malkani, S., Choi, S. Y., Takahashi, R. H., Zhang, D., Gouras, G. K., Kirkwood, A., Morris, R. G., and Shen, J. (2005). Conditional inactivation of presenilin-1 prevents amyloid accumulation and temporarily rescues contextual and spatial working memory impairments in amyloid precursor protein transgenic mice. J. Neurosci. 25, 6755-6764.
83. Saura, C. A., Choi, S. Y., Beglopoulos, V., Malkani, S., Zhang, D., Shankaranarayana Rao, B. S., Chattarji, S., Kelleher, R. J. III, Kandel, E. R., Duff, K., Kirkwood, A., and Shen, J. (2004). Loss of presenilin function causes impairments of memory and synaptic plasticity followed by age-dependent neurodegeneration. Neuron 42, 23-36.
84. Saura, C. A., Tomita, T., Davenport, F., Harris, C. L., Iwatsubo, T., and Thinakaran, G. (1999). Evidence that intramolecular associations between presenilin domains are obligatory for endoproteolytic processing. J. Biol. Chem. 274, 13818-13823.
85. Selkoe, D. J. (2002). Alzheimer's disease is a synaptic failure. Science 298, 789-791.
86. Shen, J., and Kelleher R. J. III. (2007). The presenilin hypothesis of Alzheimer's disease: evidence for a loss-of-function pathogenic mechanism. Proc. Natl. Acad. Sci. U.S.A. 104, 403-409.
87. Shepherd, C., McCann, H., and Halliday, G. M. (2009). Variations in the neuropathology of familial Alzheimer's disease. Acta Neuropathol. 118, 37-52.
88. Shepherd, C. E., Grace, E. M., Mann, D. M., and Halliday, G. M. (2007). Relationship between neuronal loss and 'inflammatory plaques' in early onset alzheimer's disease. Neuropathol. Appl. Neurobiol. 33, 328-333.
89. Shepherd, C. E., Gregory, G. C., Vickers, J. C., and Halliday, G. M. (2005). Novel 'inflammatory plaque' pathology in presenilin-1 Alzheimer's disease. Neuropathol. Appl. Neurobiol. 31, 503-511.
90. Sherrington, R., Rogaev, E. I., Liang, Y., Rogaeva, E. A., Levesque, G., Ikeda, M., Chi, H., Lin, C., Li, G., Holman, K., Tsuda, T., Mar, L., Foncin, J-F., Bruni, A. C., Montesi, M. P., Sorbi, S., Rainero, I., Pinessi, L., Nee, L., Chumakov, I., Pollen, D. A., Roses, A. D., Fraser, P. E., Rommens, J. M., and St. George-Hyslop, P. H. (1995). Cloning of a novel gene bearing missense mutations in early onset familial Alzheimer's disease. Nature 375, 754-760.
91. Shih, I. M., and Wang, T. L. (2007). Notch signaling, γ-secretase inhibitors, and cancer therapy. Cancer Res. 67, 1879-1882.
92. Sokolova, A., Hill, M. D., Rahimi, F., Warden, L. A., Halliday, G. M., and Shepherd, C. E. (2009). Monocyte chemoattractant protein-1 plays a dominant role in the chronic inflammation observed in Alzheimer's disease. Brain Pathol. 19, 392-398.
93. Stewart, W. F., Kawas, C., Corrada, M., and Metter, E. J. (1997). Risk of Alzheimer's disease and duration of NSAID use. Neurology 48, 626-632.
94. Sudo, S., Shiozawa, M., Cairns, N. J., and Wada, Y. (2005). Aberrant accentuation of neurofibrillary degeneration in the hippocampus of Alzheimer's disease with amyloid precursor protein 717 and presenilin-1 gene mutations. J. Neurol. Sci. 234, 55-65.
95. Szekely, C. A., Green, R. C., Breitner, J. C., Ostbye, T., Beiser, A. S., Corrada, M. M., Dodge, H. H., Ganguli, M., Kawas, C. H., Kuller, L. H., Psaty, B. M., Resnick, S. M., Wolf, P. A., Zonderman, A. B., Welsh-Bohmer, K. A., and Zandi, P. P. (2008). No advantage of Aβ42-lowering NSAIDs for prevention of Alzheimer dementia in six pooled cohort studies. Neurology 70, 2291-2298.
96. Takasugi, N., Tomita, T., Hayashi, I., Tsuruoka, M., Niimura, M., Takahashi, Y., Thinakaran, G., and Iwatsubo, T. (2003). The role of presenilin cofactors in the γ-secretase complex. Nature 422, 438-441.
97. Tenner, A. J. (2001). Complement in Alzheimer's disease: opportunities for modulating protective and pathogenic events. Neurobiol. Aging 22, 849-861.
98. Thinakaran, G., Borchelt, D. R., Lee, M. K., Slunt, H. H., Spitzer, L., Kim, G., Rotovitsky, T., Davenport, F., Nordstedt, C., Seeger, M., Hardy, J., Levey, A. I., Gandy, S. E., Jenkins, N. A., Copeland, N. G., Price, D. L., and Sisodia, S. S. (1996). Endoproteolysis of presenilin 1 and accumulation of processed derivatives in vivo. Neuron 17, 181-190.
99. Tournoy, J., Bossuyt, X., Snellinx, A., Regent, M., Garmyn, M., Serneels, L., Saftig, P., Craessaerts, K., De Strooper, B., and Hartmann, D. (2004). Partial loss of presenilins causes seborrheic keratosis and autoimmune disease in mice. Hum. Mol. Genet. 13, 1321-1331.
100. Vlad, S. C., Miller, D. R., Kowall, N. W., and Felson, D. T. (2008). Protective effects of NSAIDs on the development of Alzheimer disease. Neurology 70, 1672-1677.
101. Weggen, S., Diehlmann, A., Buslei, R., Beyreuther, K., and Bayer, T. A. (1998). Prominent expression of presenilin-1 in senile plaques and reactive astrocytes in Alzheimer's disease brain. Neuroreport 9, 3279-3283.
102. Weggen, S., Eriksen, J. L., Das, P., Sagi, S. A., Wang, R., Pietrzik, C. U., Findlay, K. A., Smith, T. E., Murphy, M. P., Bulter, T., Kang, D. E., Marquez-Sterling, N., Golde, T. E., and Koo, E. H. (2001). A subset of NSAIDs lower amyloidogenic Aβ42 independently of cyclooxygenase activity. Nature 414, 212-216.
103. Weggen, S., Rogers, M., and Eriksen, J. (2007). NSAIDs: small molecules for prevention of Alzheimer's disease or precursors for future drug development? Trends Pharmacol. Sci. 28, 536-543.
104. Weyand, N. J., Calton, C. M., Higashi, D. L., Kanack, K. J., and So, M. (2010). Presenilin/γ-secretase cleaves CD46 in response to Neisseria infection. J. Immunol. 184, 694-701.
105. Woodhouse, A., Shepherd, C. E., Sokolova, A., Carroll, V. L., King, A. E., Halliday, G. M., Dickson, T. C., and Vickers, J. C. (2009). Cytoskeletal alterations differentiate presenilin-1 and sporadic Alzheimer's disease. Acta Neuropathol. 117, 19-29.
106. Wyss-Coray, T., Lin, C., Yan, F., Yu, G.-Q., Rohde, M., McConlogue, L., Masliah, E., and Mucke, L. (2001). TGF-β1 promotes microglial amyloid-β clearance and reduces plaque burden in transgenic mice. Nat. Med. 7, 612-618.
107. Wyss-Coray, T., Loike, J. D., Brionne, T. C., Lu, E., Anankov, R., Yan, F., Silverstein, S. C., and Husemann, J. (2003). Adult mouse astrocytes degrade amyloid-β in vitro and in situ. Nat. Med. 9, 453-457.
108. Yagi, T., Giallourakis, C., Mohanty, S., Scheidig, C., Shen, J., Zheng, H., Xavier, R. J., and Shaw, A. C. (2008). Defective signal transduction in B lymphocytes lacking presenilin proteins. Proc. Natl. Acad. Sci. U.S.A. 105, 979-984.
109. Yan, Q., Zhang, J., Liu, H., Babu-Khan, S., Vassar, R., Biere, A. L., Citron, M., and Landreth, G. (2003). Anti-inflammatory drug therapy alters β-amyloid processing and deposition in an animal model of Alzheimer's disease. J. Neurosci. 23, 7504-7509.
110. Zekanowski, C., Golan, M. P., Krzysko, K. A., Lipczynska-Lojkowska, W., Filipek, S., Kowalska, A., Rossa, G., Peplonska, B., Styczynska, M., Maruszak, A., Religa, D., Wender, M., Kulczycki, J., Barcikowska, M., and Kuznicki, J. (2006). Two novel presenilin 1 gene mutations connected with frontotemporal dementia-like clinical phenotype: genetic and bioinformatic assessment. Exp. Neurol. 200, 82-88.
111. Zhang, Z., Nadeau, P., Song, W., Donoviel, D., Yuan, M., Bernstein, A., and Yankner, B. (2000). Presenilins are required for γ-secretase cleavage of β-APP and transmembrane cleavage of Notch-1. Nat. Cell Biol. 2, 463.