γ-Secretase, notch, Aβ and alzheimer's disease: Where do the presenilins fit in?
10.1038/nrn785
Crossref journal-article
Springer Science and Business Media LLC
Nature Reviews Neuroscience (297)
Bibliography

Sisodia, S. S., & St George-Hyslop, P. H. (2002). γ-Secretase, notch, Aβ and alzheimer’s disease: Where do the presenilins fit in? Nature Reviews Neuroscience, 3(4), 281–290.

Authors 2
  1. Sangram S. Sisodia (first)
  2. Peter H. St George-Hyslop (additional)
References 137 Referenced 435
  1. Price, D. L. & Sisodia, S. S. Mutant genes in familial Alzheimer's disease and transgenic models. Annu. Rev. Neurosci. 21, 479–505 (1998). (10.1146/annurev.neuro.21.1.479) / Annu. Rev. Neurosci. by DL Price (1998)
  2. Schenk, D. et al. Immunization with Aβ attenuates Alzheimer's disease-like pathology in the PDAPP mouse. Nature 400, 173–177 (1999). (10.1038/22124) / Nature by D Schenk (1999)
  3. Bard, F. et al. Peripherally administered antibodies against amyloid β-peptide enter the central nervous system and reduce pathology in a mouse model of Alzheimer disease. Nature Med. 6, 916–919 (2000). (10.1038/78682) / Nature Med. by F Bard (2000)
  4. Janus, C. et al. Aβ-immunization reduces behavioural impairment and dense-cored plaques in a model of Alzheimer's disease. Nature 408, 979–982 (2000). (10.1038/35050110) / Nature by C Janus (2000)
  5. Morgan, D. et al. Aβ peptide vaccination prevents memory loss in an animal model of Alzheimer's disease. Nature 408, 982–985 (2000).References 2–5 describe the use of Aβ peptides as a vaccine to generate antibodies that facilitate the clearance of Alzheimer's-disease-like neuropathology and cognitive deficits in transgenic mouse models of Alzheimer's disease. (10.1038/35050116) / Nature by D Morgan (2000)
  6. Fraser, P. E., Darabie, A. A. & McLaurin, J. A. Amyloid-β interactions with chondroitin sulfate-derived monosaccharides and disaccharides. Implications for drug development. J. Biol. Chem. 276, 6412–6419 (2001). (10.1074/jbc.M008128200) / J. Biol. Chem. by PE Fraser (2001)
  7. Soto, C. et al. β-Sheet breaker peptides inhibit fibrillogenesis in a rat brain model of amyloidosis: implications for Alzheimer's therapy. Nature Med. 4, 822–826 (1998). (10.1038/nm0798-822) / Nature Med. by C Soto (1998)
  8. Kisilevsky, R. et al. Arresting amyloidosis in vivo using small-molecule anionic sulphonates or sulphates: implications for Alzheimer's disease. Nature Med. 1, 143–148 (1995). (10.1038/nm0295-143) / Nature Med. by R Kisilevsky (1995)
  9. Brown, M. S., Ye, J., Rawson, R. B. & Goldstein, J. L. Regulated intramembrane proteolysis: a control mechanism conserved from bacteria to humans. Cell 100, 391–398 (2000). (10.1016/S0092-8674(00)80675-3) / Cell by MS Brown (2000)
  10. Kang, J. et al. The precursor of Alzheimer's disease amyloid A4 protein resembles a cell-surface receptor. Nature 325, 733–736 (1987). (10.1038/325733a0) / Nature by J Kang (1987)
  11. Goldgaber, D. et al. Characterization and chromosomal localization of a cDNA encoding brain amyloid of Alzheimer's disease. Science 235, 877–880 (1987). (10.1126/science.3810169) / Science by D Goldgaber (1987)
  12. Robakis, N. K. et al. in Disorders of the Developing Nervous System: Changing Views on their Origins, Diagnoses and Treatments (ed. Swann, J. W.) 183–193 (Alan R. Liss, New York, 1988). / Disorders of the Developing Nervous System: Changing Views on their Origins, Diagnoses and Treatments by NK Robakis (1988)
  13. Tanzi, R. E. et al. Amyloid β-protein gene: cDNA, mRNA distribution and genetic linkage near the Alzheimer locus. Science 235, 880–884 (1987). (10.1126/science.2949367) / Science by RE Tanzi (1987)
  14. Kitaguchi, N., Takahashi, Y., Tokushima, Y., Shiojiri, S. & Ito, H. Novel precursor of Alzheimer's disease amyloid protein shows protease inhibitory activity. Nature 331, 530–532 (1988). (10.1038/331530a0) / Nature by N Kitaguchi (1988)
  15. Weidemann, A. et al. Identification, biogenesis, and localization of precursors of Alzheimer disease A4 amyloid protein. Cell 57, 115–126 (1989). (10.1016/0092-8674(89)90177-3) / Cell by A Weidemann (1989)
  16. Haass, C., Koo, E. H., Mellon, A., Hung, A. Y. & Selkoe, D. J. Targeting of cell-surface β-amyloid precursor protein to lysosomes: alternative processing into amyloid-bearing fragments. Nature 357, 500–503 (1992). (10.1038/357500a0) / Nature by C Haass (1992)
  17. Sisodia, S. S. Secretion of the β-amyloid precursor protein. Ann. NY Acad. Sci. 674, 53–57 (1992). (10.1111/j.1749-6632.1992.tb27476.x) / Ann. NY Acad. Sci. by SS Sisodia (1992)
  18. Hung, A. Y. & Selkoe, D. J. Selective ectodomain phosphorylation and regulated cleavage of β-amyloid precursor protein. EMBO J. 13, 534–542 (1994). (10.1002/j.1460-2075.1994.tb06291.x) / EMBO J. by AY Hung (1994)
  19. Walter, J. et al. Ectodomain phosphorylation of β-amyloid precursor protein at two distinct cellular locations. J. Biol. Chem. 272, 1896–1903 (1997). (10.1074/jbc.272.3.1896) / J. Biol. Chem. by J Walter (1997)
  20. Zheng, H. et al. Mice deficient for the amyloid precursor protein gene. Ann. NY Acad. Sci. 777, 421–426 (1996). (10.1111/j.1749-6632.1996.tb34456.x) / Ann. NY Acad. Sci. by H Zheng (1996)
  21. Saitoh, T. et al. Secreted form of amyloid β-protein is involved in the growth regulation of fibroblasts. Cell 58, 615–622 (1989). (10.1016/0092-8674(89)90096-2) / Cell by T Saitoh (1989)
  22. Milward, A. E. et al. The amyloid protein precursor of Alzheimer disease is a mediator of the effects of NGF on neurite outgrowth. Neuron 9, 129–137 (1992). (10.1016/0896-6273(92)90228-6) / Neuron by AE Milward (1992)
  23. Nishimoto, I. et al. Alzheimer amyloid protein precursor complexes with brain GTP-binding protein Go. Nature 362, 75–79 (1993). (10.1038/362075a0) / Nature by I Nishimoto (1993)
  24. Kamal, A., Almenar-Queralt, A., LeBlanc, J. F., Roberts, E. A. & Goldstein, L. S. Kinesin-mediated axonal transport of a membrane compartment containing β-secretase and presenilin-1 requires APP. Nature 414, 643–648 (2001). (10.1038/414643a) / Nature by A Kamal (2001)
  25. Cao, X. & Sudhof, T. C. A transcriptionally active complex of APP with Fe65 and histone acetyltransferase Tip60. Science 293, 115–120 (2001). (10.1126/science.1058783) / Science by X Cao (2001)
  26. Sastre, M. et al. Presenilin-dependent γ-secretase processing of β-amyloid precursor protein at a site corresponding to the S3 cleavage of Notch. EMBO Rep. 2, 835–841 (2001). (10.1093/embo-reports/kve180) / EMBO Rep. by M Sastre (2001)
  27. Cupers, P., Orlans, I., Craessaerts, K., Annaert, W. & De Strooper, B. The amyloid precursor protein (APP)-cytoplasmic fragment generated by γ-secretase is rapidly degraded but distributes partially in a nuclear fraction of neurones in culture. J. Neurochem. 78, 1168–1178 (2001). (10.1046/j.1471-4159.2001.00516.x) / J. Neurochem. by P Cupers (2001)
  28. Palmert, M. R. et al. The β-amyloid protein precursor of Alzheimer disease has soluble derivatives found in human brain and cerebrospinal fluid. Proc. Natl Acad. Sci. USA 86, 6338–6342 (1989). (10.1073/pnas.86.16.6338) / Proc. Natl Acad. Sci. USA by MR Palmert (1989)
  29. Esch, F. S. et al. Cleavage of amyloid β-peptide during constitutive processing of its precursor. Science 248, 1122–1124 (1990). (10.1126/science.2111583) / Science by FS Esch (1990)
  30. Sisodia, S. S., Koo, E. H., Beyreuther, K., Unterbeck, A. & Price, D. Evidence that β-amyloid protein in Alzheimer's disease is not derived by normal processing. Science 248, 492–495 (1990). (10.1126/science.1691865) / Science by SS Sisodia (1990)
  31. Wang, R., Meschia, J. F., Cotter, R. J. & Sisodia, S. S. Secretion of the β/A4 amyloid precursor protein. Identification of a cleavage site in cultured mammalian cells. J. Biol. Chem. 266, 16960–16964 (1991). (10.1016/S0021-9258(18)55397-7) / J. Biol. Chem. by R Wang (1991)
  32. Sahasrabudhe, S. R. et al. Enzymatic generation of the amino terminus of the β-amyloid peptide. J. Biol. Chem. 268, 16699–16705 (1993). (10.1016/S0021-9258(19)85474-1) / J. Biol. Chem. by SR Sahasrabudhe (1993)
  33. Buxbaum, J. D. et al. Evidence that tumor necrosis factor-α converting enzyme is involved in regulated α-secretase cleavage of the Alzheimer amyloid protein precursor. J. Biol. Chem. 273, 27765–27767 (1998). (10.1074/jbc.273.43.27765) / J. Biol. Chem. by JD Buxbaum (1998)
  34. Nitsch, R. M., Slack, B. E., Wurtman, R. J. & Growden, J. H. Release of Alzheimer amyloid precursor derivatives stimulated by activation of muscarinic acetylcholine receptors. Science 258, 304–307 (1992). (10.1126/science.1411529) / Science by RM Nitsch (1992)
  35. Xu, H., Greengard, P. & Gandy, S. Regulated formation of Golgi secretory vesicles containing Alzheimer β-amyloid precursor protein. J. Biol. Chem. 270, 23243–23245 (1995). (10.1074/jbc.270.40.23243) / J. Biol. Chem. by H Xu (1995)
  36. Parvathy, S., Karran, E. H., Turner, A. J. & Hooper, N. M. The secretases that cleave angiotensin converting enzyme and the amyloid precursor protein are distinct from tumour necrosis factor-α convertase. FEBS Lett. 431, 63–65 (1998). (10.1016/S0014-5793(98)00726-1) / FEBS Lett. by S Parvathy (1998)
  37. Lammich, S. et al. Constitutive and regulated α-secretase cleavage of Alzheimer's amyloid precursor protein by a disintegrin metalloprotease. Proc. Natl Acad. Sci. USA 96, 3922–3927 (1999).References 33–37 show that α-secretase cleavage is a physiological, regulated cleavage of APP, and that TACE and other members of the ADAM superfamily are good candidates for this enzymatic activity. (10.1073/pnas.96.7.3922) / Proc. Natl Acad. Sci. USA by S Lammich (1999)
  38. Vassar, R. et al. β-Secretase cleavage of Alzheimer's amyloid precursor protein by the transmembrane aspartic protease BACE. Science 286, 735–741 (1999). (10.1126/science.286.5440.735) / Science by R Vassar (1999)
  39. Hussain, I. et al. Identification of a novel aspartic protease (Asp2) as β-secretase. Mol. Cell. Neurosci. 14, 419–427 (1999). (10.1006/mcne.1999.0811) / Mol. Cell. Neurosci. by I Hussain (1999)
  40. Sinha, S. et al. Purification and cloning of amyloid precursor protein β-secretase from human brain. Nature 402, 537–540 (1999). (10.1038/990114) / Nature by S Sinha (1999)
  41. Yan, R. et al. Membrane-anchored aspartyl protease with Alzheimer's disease β-secretase activity. Nature 402, 533–537 (1999).References 38–41 describe the cloning of β-secretase as a type 1 transmembrane aspartyl protease. (10.1038/990107) / Nature by R Yan (1999)
  42. Shoji, M. et al. Production of the Alzheimer amyloid β protein by normal proteolytic processing. Science 258, 126–129 (1992). (10.1126/science.1439760) / Science by M Shoji (1992)
  43. Haass, C. et al. Amyloid β-peptide is produced by cultured cells during normal metabolism. Nature 359, 322–325 (1992).References 42 and 43 show that Aβ production is a physiological event in many cell types. (10.1038/359322a0) / Nature by C Haass (1992)
  44. Jarrett, J. T. & Lansbury, P. T. Seeding one-dimensional crystallization of amyloid: a pathogenic mechanism in Alzheimer's disease and scrapie? Cell 73, 1055–1058 (1993). (10.1016/0092-8674(93)90635-4) / Cell by JT Jarrett (1993)
  45. Yankner, B. A., Duffy, L. K. & Kirschner, D. A. Neurotrophic and neurotoxic effects of amyloid β protein: reversal by tachykinin neuropeptides. Science 250, 279–282 (1990). (10.1126/science.2218531) / Science by BA Yankner (1990)
  46. Pike, C. J., Burdick, D., Walencewicz, A. J., Glabe, C. G. & Cotman, C. W. Neurodegeneration induced by β-amyloid peptides in vitro: the role of peptide assembly state. J. Neurosci. 13, 1676–1678 (1993). (10.1523/JNEUROSCI.13-04-01676.1993) / J. Neurosci. by CJ Pike (1993)
  47. Lorenzo, A. & Yanker, B. A. β-Amyloid neurotoxicity requires fibril formation and is inhibited by Congo red. Proc. Natl Acad. Sci. USA 91, 12243–12247 (1994). (10.1073/pnas.91.25.12243) / Proc. Natl Acad. Sci. USA by A Lorenzo (1994)
  48. Koo, E. H. & Squazzo, S. L. Evidence that production and release of amyloid β-protein precursor involves the endocytic pathway. J. Biol. Chem. 269, 17386–17389 (1994). (10.1016/S0021-9258(17)32449-3) / J. Biol. Chem. by EH Koo (1994)
  49. Koo, E. H., Squazzo, S. L., Selkoe, D. J. & Koo, C. H. Trafficking of cell-surface amyloid β-protein precursor. I. Secretion, endocytosis and recycling as detected by labeled monoclonal antibody. J. Cell Sci. 109, 991–998 (1996). (10.1242/jcs.109.5.991) / J. Cell Sci. by EH Koo (1996)
  50. Cook, D. G. et al. Alzheimer Aβ1–42 peptide is generated in the endoplasmic reticulum/intermediate compartment of NT2N cells. Nature Med. 3, 1021–1023 (1997). (10.1038/nm0997-1021) / Nature Med. by DG Cook (1997)
  51. Hartmann, T. et al. Distinct sites of intracellular production for Alzheimer's disease Aβ40/42 amyloid peptides. Nature Med. 3, 1016–1020 (1997). (10.1038/nm0997-1016) / Nature Med. by T Hartmann (1997)
  52. Citron, M. et al. Evidence that the 42- and 40-amino-acid forms of amyloid β protein are generated from the β-amyloid precursor protein by different protease activities. Proc. Natl Acad. Sci. USA 93, 13170–13175 (1996). (10.1073/pnas.93.23.13170) / Proc. Natl Acad. Sci. USA by M Citron (1996)
  53. Yasojima, K., Akiyama, H., McGeer, E. G. & McGeer, P. L. Reduced neprilysin in high plaque areas of Alzheimer brain: a possible relationship to deficient degradation of β-amyloid peptide. Neurosci. Lett. 297, 97–100 (2001). (10.1016/S0304-3940(00)01675-X) / Neurosci. Lett. by K Yasojima (2001)
  54. Qiu, W. Q. et al. Insulin-degrading enzyme regulates extracellular levels of amyloid β-protein by degradation. J. Biol. Chem. 273, 32730–32738 (1998). (10.1074/jbc.273.49.32730) / J. Biol. Chem. by WQ Qiu (1998)
  55. Chesneau, V., Vekrellis, K., Rosner, M. R. & Selkoe, D. J. Purified recombinant insulin-degrading enzyme degrades amyloid β-protein but does not promote its oligomerization. Biochem. J. 351, 509–516 (2000). (10.1042/bj3510509) / Biochem. J. by V Chesneau (2000)
  56. Goate, A. M. et al. Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer disease. Nature 349, 704–706 (1991). (10.1038/349704a0) / Nature by AM Goate (1991)
  57. Sherrington, R. et al. Cloning of a gene bearing missense mutations in early onset familial Alzheimer's disease. Nature 375, 754–760 (1995). (10.1038/375754a0) / Nature by R Sherrington (1995)
  58. Levy-Lahad, E. et al. A familial Alzheimer's disease locus on chromosome 1. Science 269, 970–973 (1995). (10.1126/science.7638621) / Science by E Levy-Lahad (1995)
  59. Rogaev, E. I. et al. Familial Alzheimer's disease in kindreds with missense mutations in a novel gene on chromosome 1 related to the Alzheimer's disease type 3 gene. Nature 376, 775–778 (1995).References 56–59 describe the discovery of disease-causing mutations in the APP, PS1 and PS2 genes. (10.1038/376775a0) / Nature by EI Rogaev (1995)
  60. Citron, M. et al. Mutation of the β-amyloid precursor protein in familial Alzheimer's disease increases β-protein production. Nature 360, 672–674 (1992). (10.1038/360672a0) / Nature by M Citron (1992)
  61. Haass, C., Hung, A. Y., Selkoe, D. J. & Teplow, D. B. Mutations associated with a locus for familial Alzheimer's disease result in alternative processing of amyloid β-protein precursor. J. Biol. Chem. 269, 17741–17748 (1994). (10.1016/S0021-9258(17)32503-6) / J. Biol. Chem. by C Haass (1994)
  62. Scheuner, D. et al. Secreted amyloid-β protein similar to that in the senile plaques of Alzheimer disease is increased in vivo by presenilin 1 and 2 and APP mutations linked to FAD. Nature Med. 2, 864–870 (1996). (10.1038/nm0896-864) / Nature Med. by D Scheuner (1996)
  63. Borchelt, D. R. et al. Familial Alzheimer's disease linked presenilin 1 variants elevate Aβ1–42/1–40 ratio in vitro and in vivo. Neuron 17, 1005–1013 (1996). (10.1016/S0896-6273(00)80230-5) / Neuron by DR Borchelt (1996)
  64. Duff, K. et al. Increased amyloid-β42(43) in brains of mice expressing mutant presenilin 1. Nature 383, 710–713 (1996). (10.1038/383710a0) / Nature by K Duff (1996)
  65. Citron, M. et al. Mutant presenilins of Alzheimer's disease increase production of 42-residue amyloid β-protein in both transfected cells and transgenic mice. Nature Med. 3, 67–72 (1997).References 60–65 describe the discovery that disease-causing mutations in APP, PS1 and PS2 all alter the processing of APP and/or of Aβ itself, causing accumulation of neurotoxic derivatives. (10.1038/nm0197-67) / Nature Med. by M Citron (1997)
  66. L'Hernault, S. W. L. & Arduengo, P. M. Mutation of a putative sperm membrane protein in Caenorhabditis elegans prevents sperm differentiation but not its associated meiotic divisions. J. Cell Biol. 119, 55–69 (1992). (10.1083/jcb.119.1.55) / J. Cell Biol. by SWL L'Hernault (1992)
  67. Levitan, D. & Greenwald, I. Facilitation of lin-12-mediated signalling by sel-12, a Caenorhabditis elegans S182 Alzheimer's disease gene. Nature 377, 351–354 (1995). (10.1038/377351a0) / Nature by D Levitan (1995)
  68. Li, X. & Greenwald, I. HOP-1, a Caenorhabditis elegans presenilin, appears to be functionally redundant with SEL-12 presenilin and to facilitate LIN-12 and GLP-1 signalling. Proc. Natl Acad. Sci. USA 94, 12204–12209 (1997). (10.1073/pnas.94.22.12204) / Proc. Natl Acad. Sci. USA by X Li (1997)
  69. Doan, A. et al. Protein topology of presenilin 1. Neuron 17, 1023–1030 (1996). (10.1016/S0896-6273(00)80232-9) / Neuron by A Doan (1996)
  70. Li, X. & Greenwald, I. Membrane topology of the C. elegans SEL-12 presenilin. Neuron 17, 1015–1021 (1996). (10.1016/S0896-6273(00)80231-7) / Neuron by X Li (1996)
  71. De Strooper, B. et al. Phosphorylation, subcellular localization, and membrane orientation of the Alzheimer's disease-associated presenilins. J. Biol. Chem. 272, 3590–3598 (1997). (10.1074/jbc.272.6.3590) / J. Biol. Chem. by B De Strooper (1997)
  72. Thinakaran, G. et al. Endoproteolysis of presenilin 1 and accumulation of processed derivatives in vivo. Neuron 17, 181–190 (1996). (10.1016/S0896-6273(00)80291-3) / Neuron by G Thinakaran (1996)
  73. Lee, M. K. et al. Hyperaccumulation of FAD-linked presenilin-1 variants in vivo. Nature Med. 3, 756–760 (1997). (10.1038/nm0797-756) / Nature Med. by MK Lee (1997)
  74. Thinakaran, G. et al. Evidence that levels of presenilins (PS1 and PS2) are coordinately regulated by competition for limiting cellular factors. J. Biol. Chem. 272, 28415–28422 (1997). (10.1074/jbc.272.45.28415) / J. Biol. Chem. by G Thinakaran (1997)
  75. Yu, G. et al. The presenilin 1 protein is a component of a high molecular weight intracellular complex that contains β-catenin. J. Biol. Chem. 273, 16470–16475 (1998). (10.1074/jbc.273.26.16470) / J. Biol. Chem. by G Yu (1998)
  76. Thinakaran, G. et al. Stable association of the presenilin derivatives and absence of presenilin interactions with APP. Neurobiol. Dis. 4, 438–453 (1998). (10.1006/nbdi.1998.0171) / Neurobiol. Dis. by G Thinakaran (1998)
  77. Capell, A. et al. The proteolytic fragments of the Alzheimer's disease associated presenilin-1 form heterodimers and occur as a 100–150 kDa molecular mass complex. J. Biol. Chem. 273, 3205–3211 (1998). (10.1074/jbc.273.6.3205) / J. Biol. Chem. by A Capell (1998)
  78. Li, Y.-M. et al. Presenilin 1 is linked with γ-secretase activity in the detergent solubilized state. Proc. Natl Acad. Sci. USA 97, 6138–6143 (2000).References 75–78 describe the discovery that PS1 is part of a multimeric, high-molecular-weight protein complex. (10.1073/pnas.110126897) / Proc. Natl Acad. Sci. USA by Y-M Li (2000)
  79. Walter, J. et al. The Alzheimer's disease associated presenilins are differentially phosphorylated proteins located predominantly within the endoplasmic reticulum. Mol. Med. 2, 673–691 (1996). (10.1007/BF03401652) / Mol. Med. by J Walter (1996)
  80. Annaert, W. G. et al. Presenilin 1 controls γ-secretase processing of amyloid precursor protein in pre-Golgi compartments of hippocampal neurons. J. Cell Biol. 147, 277–294 (1999). (10.1083/jcb.147.2.277) / J. Cell Biol. by WG Annaert (1999)
  81. Cupers, P. et al. The discrepancy between presenilin subcellular localization and γ-secretase processing of amyloid precursor protein. J. Cell Biol. 154, 731–740 (2001). (10.1083/jcb.200104045) / J. Cell Biol. by P Cupers (2001)
  82. Ray, W. J. et al. Cell surface presenilin 1 participates in the γ-secretase-like proteolysis of Notch. J. Biol. Chem. 274, 36801–36807 (1999). (10.1074/jbc.274.51.36801) / J. Biol. Chem. by WJ Ray (1999)
  83. Baki, L. et al. Presenilin-1 binds cytoplasmic epithelial cadherin, inhibits cadherin/p120 association, and regulates stability and function of the cadherin/catenin adhesion complex. Proc. Natl Acad. Sci. USA 98, 2381–2386 (2001). (10.1073/pnas.041603398) / Proc. Natl Acad. Sci. USA by L Baki (2001)
  84. Georgakopoulos, A. et al. Presenilin-1 forms complexes with the cadherin/catenin cell–cell adhesion system and is recruited to intercellular and synaptic contacts. Mol. Cell 4, 893–902 (1999). (10.1016/S1097-2765(00)80219-1) / Mol. Cell by A Georgakopoulos (1999)
  85. Chung, H.-M. & Struhl, G. Nicastrin is required for Presenilin-mediated transmembrane cleavage in Drosophila. Nature Cell Biol. 3, 1129–1132 (2001). (10.1038/ncb1201-1129) / Nature Cell Biol. by H-M Chung (2001)
  86. Zhou, J. et al. Presenilin 1 interacts with a novel member of the armadillo family. Neuroreport 8, 2085–2090 (1997). (10.1097/00001756-199705260-00054) / Neuroreport by J Zhou (1997)
  87. Levesque, G. et al. Presenilins interact with armadillo proteins including neural specific plakophilin related protein and β-catenin. J. Neurochem. 72, 999–1008 (1999). (10.1046/j.1471-4159.1999.0720999.x) / J. Neurochem. by G Levesque (1999)
  88. Yu, G. et al. Nicastrin modulates presenilin-mediated notch/glp-1 and βAPP processing. Nature 407, 48–54 (2000).Describes the discovery of a protein that is a component of the presenilin complex. (10.1038/35024009) / Nature by G Yu (2000)
  89. Saura, C. A. et al. The nonconserved hydrophilic loop domain of presenilin (PS) is not required for PS endoproteolysis or enhanced Aβ42 production mediated by familial early onset Alzheimer's disease-linked PS variants. J. Biol. Chem. 275, 17136–17142 (2000). (10.1074/jbc.M909624199) / J. Biol. Chem. by CA Saura (2000)
  90. Ho, C. et al. δ-Catenin is a nervous system-specific adherens junction protein which undergoes dynamic relocalization during development. J. Comp. Neurol. 420, 261–276 (2000). (10.1002/(SICI)1096-9861(20000501)420:2<261::AID-CNE8>3.0.CO;2-Q) / J. Comp. Neurol. by C Ho (2000)
  91. Lu, Q. et al. δ-Catenin, an adhesive junction-associated protein which promotes cell scattering. J. Cell Biol. 144, 519–532 (1999). (10.1083/jcb.144.3.519) / J. Cell Biol. by Q Lu (1999)
  92. Goutte, C., Hepler, W., Mickey, K. M. & Priess, J. R. aph-2 encodes a novel extracellular protein required for GLP-1-mediated signaling. Development 127, 2481–2492 (2000). (10.1242/dev.127.11.2481) / Development by C Goutte (2000)
  93. Levitan, D., Yu, G., St George-Hyslop, P. & Goutte, C. APH-2/Nicastrin functions in LIN-12/Notch signalling in the C. elegans somatic gonad. Dev. Biol. 240, 654–661 (2001). (10.1006/dbio.2001.0486) / Dev. Biol. by D Levitan (2001)
  94. Lopez-Schier, H. & St Johnston, D. S. Drosophila Nicastrin is essential for the intramembranous cleavage of Notch. Dev. Cell 2, 79–89 (2002). (10.1016/S1534-5807(01)00109-5) / Dev. Cell by H Lopez-Schier (2002)
  95. Hu, Y., Ye, Y. & Fortini, M. E. Nicastrin is required for γ-secretase cleavage of the Drosophila Notch receptor. Dev. Cell 2, 69–78 (2002). (10.1016/S1534-5807(01)00105-8) / Dev. Cell by Y Hu (2002)
  96. Chen, F. et al. Nicastrin binds to membrane-tethered Notch. Nature Cell Biol. 3, 751–754 (2001). (10.1038/35087069) / Nature Cell Biol. by F Chen (2001)
  97. De Strooper, B. et al. Deficiency of presenilin 1 inhibits the normal cleavage of amyloid precursor protein. Nature 391, 387–390 (1998). (10.1038/34910) / Nature by B De Strooper (1998)
  98. Naruse, S. et al. Effect of PS1 deficiency on membrane protein trafficking in neurons. Neuron 21, 1213–1221 (1998). (10.1016/S0896-6273(00)80637-6) / Neuron by S Naruse (1998)
  99. Chen, F. et al. Proteolytic derivative of amyloid precursor protein accumulate in restricted and unpredicted intracellular compartments in the absence of functional presenilin 1 expression. J. Biol. Chem. 275, 36794–36802 (2000). (10.1074/jbc.M006986200) / J. Biol. Chem. by F Chen (2000)
  100. Herreman, A. et al. Total inactivation of γ-secretase activity in presenilin-deficient embryonic stem cells. Nature Cell Biol. 2, 461–462 (2000). (10.1038/35017105) / Nature Cell Biol. by A Herreman (2000)
  101. Zhang, Z. et al. Presenilins are required for γ-secretase cleavage of β-APP and transmembrane cleavage of Notch-1. Nature Cell Biol. 2, 463–465 (2000).References 97–101, 108–113 and 115–117 describe the discovery that PS1 (and the other components of the multimeric PS1 complex) are required for the cleavage of APP, ErbB4 and Notch within their transmembrane domains. (10.1038/35017108) / Nature Cell Biol. by Z Zhang (2000)
  102. Brou, C. et al. A novel proteolytic cleavage involved in Notch signaling: the role of the disintegrin-metalloprotease TACE. Mol. Cell 5, 207–216 (2000). (10.1016/S1097-2765(00)80417-7) / Mol. Cell by C Brou (2000)
  103. Mumm, J. S. et al. A ligand-induced extracellular cleavage regulates γ-secretase-like proteolytic activation of Notch1. Mol. Cell 5, 197–206 (2000). (10.1016/S1097-2765(00)80416-5) / Mol. Cell by JS Mumm (2000)
  104. Sisodia, S. S. β-Amyloid precursor protein cleavage by a membrane-bound protease. Proc. Natl Acad. Sci. USA 89, 6075–6079 (1992). (10.1073/pnas.89.13.6075) / Proc. Natl Acad. Sci. USA by SS Sisodia (1992)
  105. Schroeter, E. H., Kisslinger, J. A. & Kopan, R. Notch-1 signalling requires ligand-induced proteolytic release of intracellular domain. Nature 393, 382–386 (1998). (10.1038/30756) / Nature by EH Schroeter (1998)
  106. Weinmaster, G. Notch signal transduction: a real rip and more. Curr. Opin. Genet. Dev. 10, 363–369 (2000). (10.1016/S0959-437X(00)00097-6) / Curr. Opin. Genet. Dev. by G Weinmaster (2000)
  107. Chan, Y. M. & Jan, Y. N. Presenilins, processing of β-amyloid precursor protein, and Notch signaling. Neuron 23, 201–204 (1999). (10.1016/S0896-6273(00)80771-0) / Neuron by YM Chan (1999)
  108. Wong, P. C. et al. Presenilin 1 is required for Notch and Dll1 expression in the paraxial mesoderm. Nature 387, 288–292 (1997). (10.1038/387288a0) / Nature by PC Wong (1997)
  109. Shen, J. et al. Skeletal and CNS defects in presenilin-1 deficient mice. Cell 89, 629–639 (1997). (10.1016/S0092-8674(00)80244-5) / Cell by J Shen (1997)
  110. Donoviel, D. et al. Mice lacking both presenilin genes exhibit early embryonic patterning defects. Genes Dev. 13, 2801–2810 (1999). (10.1101/gad.13.21.2801) / Genes Dev. by D Donoviel (1999)
  111. Herreman, A. et al. Presenilin 2 deficiency causes a mild pulmonary phenotype and no changes in amyloid precursor protein processing but enhances the embryonic lethal phenotype of presenilin 1 deficiency. Proc. Natl Acad. Sci. USA 96, 11872–11877 (1999). (10.1073/pnas.96.21.11872) / Proc. Natl Acad. Sci. USA by A Herreman (1999)
  112. De Strooper, B. et al. A presenilin dependent γ-secretase-like protease mediates release of Notch intracellular domain. Nature 398, 518–522 (1999). (10.1038/19083) / Nature by B De Strooper (1999)
  113. Ni, C. Y., Murphy, M. P., Golde, T. E. & Carpenter, G. γ-Secretase cleavage and nuclear localization of ErbB-4 receptor tyrosine kinase. Science 294, 2179–2181 (2001). (10.1126/science.1065412) / Science by CY Ni (2001)
  114. Fergani, A., Yu, G., St George-Hyslop, P. & Checler, F. Wild-type and mutated nicastrins do not display aminopeptidase M- and B-like activities. Biochem. Biophys. Res. Commun. 289, 678–680 (2001). (10.1006/bbrc.2001.6030) / Biochem. Biophys. Res. Commun. by A Fergani (2001)
  115. Wolfe, M. S. et al. Two transmembrane aspartates in presenilin 1 required for presenilin endoproteolysis and γ-secretase activity. Nature 398, 513–517 (1999). (10.1038/19077) / Nature by MS Wolfe (1999)
  116. Li, Y. M. et al. Photoactivated γ-secretase inhibitors directed to the active site covalently label presenilin 1. Nature 405, 689–694 (2000). (10.1038/35015085) / Nature by YM Li (2000)
  117. Esler, W. P. et al. Transition-state analogue inhibitors of γ-secretase bind directly to presenilin-1. Nature Cell Biol. 2, 428–434 (2000). (10.1038/35017062) / Nature Cell Biol. by WP Esler (2000)
  118. Steiner, H. et al. Glycine 384 is required for presenilin-1 function and is conserved in bacterial polytopic aspartyl proteases. Nature Cell Biol. 2, 848–851 (2000). (10.1038/35041097) / Nature Cell Biol. by H Steiner (2000)
  119. Huppert, S. S. et al. Embryonic lethality in mice homozygous for a processing-deficient allele of Notch1. Nature 405, 966–970 (2000). (10.1038/35016111) / Nature by SS Huppert (2000)
  120. Lichtenthaler, S. F., Ida, N., Multhaup, G., Masters, C. L. & Beyreuther, K. Mutations in the transmembrane domain of APP altering γ-secretase specificity. Biochemistry 36, 15396–15403 (1997). (10.1021/bi971071m) / Biochemistry by SF Lichtenthaler (1997)
  121. Yu, C. et al. Characterization of a presenilin-mediated amyloid precursor protein carboxyl-terminal fragment γ. Evidence for distinct mechanisms involved in γ-secretase processing of the APP and Notch1 transmembrane domains. J. Biol. Chem. 276, 43756–43760 (2001). (10.1074/jbc.C100410200) / J. Biol. Chem. by C Yu (2001)
  122. Gu, Y. et al. Distinct intramembrane cleavage of the β-amyloid precursor protein family resembling γ-secretase-like cleavage of Notch. J. Biol. Chem. 276, 35235–35238 (2001). (10.1074/jbc.C100357200) / J. Biol. Chem. by Y Gu (2001)
  123. Kulic, L. et al. Separation of presenilin function in amyloid β-peptide generation and endoproteolysis of Notch. Proc. Natl Acad. Sci. USA 97, 5913–5918 (2000). (10.1073/pnas.100049897) / Proc. Natl Acad. Sci. USA by L Kulic (2000)
  124. Petit, A. et al. New protease inhibitors prevent γ-secretase-mediated Aβ40/42 production without affecting Notch cleavage. Nature Cell Biol. 3, 507–511 (2001). (10.1038/35074581) / Nature Cell Biol. by A Petit (2001)
  125. Kim, S. H. et al. Multiple effects of aspartate mutant presenilin 1 on the processing and trafficking of amyloid precursor protein. J. Biol. Chem. 276, 43343–43350 (2001). (10.1074/jbc.M108245200) / J. Biol. Chem. by SH Kim (2001)
  126. Capell, A. et al. Presenilin-1 differentially facilitates endoproteolysis of the β-amyloid precursor protein and Notch. Nature Cell Biol. 2, 205–211 (2000). (10.1038/35008626) / Nature Cell Biol. by A Capell (2000)
  127. Murphy, M. P. et al. Presenilin 1 regulates pharmacologically distinct γ-secretase activities. Implications for the role of presenilin in γ-secretase cleavage. J. Biol. Chem. 275, 26277–26284 (2000). (10.1074/jbc.M002812200) / J. Biol. Chem. by MP Murphy (2000)
  128. Tomita, T. et al. The first proline of PALP motif at the C terminus of presenilins is obligatory for stabilization, complex formation, and γ-secretase activities of presenilins. J. Biol. Chem. 276, 33273–33281 (2001). (10.1074/jbc.M011152200) / J. Biol. Chem. by T Tomita (2001)
  129. Yu, G. et al. Mutation of conserved aspartates affects maturation of both aspartate mutant and endogenous presenilin 1 and presenilin 2 complexes. J. Biol. Chem. 275, 27348–27353 (2000). (10.1016/S0021-9258(19)61517-6) / J. Biol. Chem. by G Yu (2000)
  130. Perez, R. G. et al. Mutagenesis identifies new signals for β-amyloid precursor protein endocytosis, turnover, and the generation of secreted fragments, including Aβ42 J. Biol. Chem. 274, 18851–18856 (1999). (10.1074/jbc.274.27.18851) / J. Biol. Chem. by RG Perez (1999)
  131. Arduengo, P. M., Appleberry, O. K., Chuang, P. & L'Hernault, S. W. The presenilin protein family member SPE-4 localizes to an ER/Golgi derived organelle and is required for proper cytoplasmic partitioning during Caenorhabditis elegans spermatogenesis. J. Cell Sci. 111, 3645–3654 (1998). (10.1242/jcs.111.24.3645) / J. Cell Sci. by PM Arduengo (1998)
  132. Annaert, W. G. et al. Interaction with telencephalin and the amyloid precursor protein predicts a ring structure for presenilins. Neuron 32, 579–589 (2001). (10.1016/S0896-6273(01)00512-8) / Neuron by WG Annaert (2001)
  133. DeBose-Boyd, R. A. et al. Transport-dependent proteolysis of SREBP: relocation of site-1 protease from Golgi to ER obviates the need for SREBP transport to Golgi. Cell 99, 703–712 (1999). (10.1016/S0092-8674(00)81668-2) / Cell by RA DeBose-Boyd (1999)
  134. Cai, H. et al. BACE1 is the major β-secretase for generation of Aβ peptides by neurons. Nature Neurosci. 4, 233–234 (2001). (10.1038/85064) / Nature Neurosci. by H Cai (2001)
  135. Wong, P. C., Price, D. L. & Cai, H. The brain's susceptibility to amyloid plaques. Science 293, 1434 (2001). (10.1126/science.293.5534.1434b) / Science by PC Wong (2001)
  136. Hadland, B. K. et al. γ-Secretase inhibitors repress thymocyte development. Proc. Natl Acad. Sci. USA 98, 7487–7491 (2001). (10.1073/pnas.131202798) / Proc. Natl Acad. Sci. USA by BK Hadland (2001)
  137. St George-Hyslop, P. H. Piecing together Alzheimer's. Sci. Am. 283, 76–83 (2000). (10.1038/scientificamerican1200-76) / Sci. Am. by PH St George-Hyslop (2000)
Dates
Type When
Created 23 years ago (July 26, 2002, 4:56 a.m.)
Deposited 2 years, 3 months ago (May 19, 2023, 12:29 a.m.)
Indexed 3 months, 1 week ago (May 15, 2025, 5:27 a.m.)
Issued 23 years, 4 months ago (April 1, 2002)
Published 23 years, 4 months ago (April 1, 2002)
Published Print 23 years, 4 months ago (April 1, 2002)
Funders 0

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@article{Sisodia_2002, title={γ-Secretase, notch, Aβ and alzheimer’s disease: Where do the presenilins fit in?}, volume={3}, ISSN={1471-0048}, url={http://dx.doi.org/10.1038/nrn785}, DOI={10.1038/nrn785}, number={4}, journal={Nature Reviews Neuroscience}, publisher={Springer Science and Business Media LLC}, author={Sisodia, Sangram S. and St George-Hyslop, Peter H.}, year={2002}, month=apr, pages={281–290} }