PS1

Summary

Gene Symbol: PS1
Description: presenilin 1
Alias: ACNINV3, AD3, FAD, PS-1, PS1, S182, presenilin-1, presenilin-1 isoform I-467
Species: human
Products:     PS1

Top Publications

  1. Gu Y, Sanjo N, Chen F, Hasegawa H, Petit A, Ruan X, et al. The presenilin proteins are components of multiple membrane-bound complexes that have different biological activities. J Biol Chem. 2004;279:31329-36 pubmed
    ..is a stable and abundant intermediate complex of approximately 440 kDa, which contains aph-1, pen-2, nicastrin, and PS1. However, it is the very low abundance, high mass (>/=670 kDa) heteromeric complexes that are associated with ..
  2. Green K, Demuro A, Akbari Y, Hitt B, Smith I, Parker I, et al. SERCA pump activity is physiologically regulated by presenilin and regulates amyloid beta production. J Cell Biol. 2008;181:1107-16 pubmed publisher
    ..We show that SERCA activity is diminished in fibroblasts lacking both PS1 and PS2 genes, despite elevated SERCA2b steady-state levels, and we show that presenilins and SERCA physically ..
  3. Pantieri R, Pardini M, Cecconi M, Dagna Bricarelli F, Vitali A, Piccini A, et al. A novel presenilin 1 L166H mutation in a pseudo-sporadic case of early-onset Alzheimer's disease. Neurol Sci. 2005;26:349-50 pubmed
  4. Guerreiro R, Baquero M, Blesa R, Boada M, Brás J, Bullido M, et al. Genetic screening of Alzheimer's disease genes in Iberian and African samples yields novel mutations in presenilins and APP. Neurobiol Aging. 2010;31:725-31 pubmed publisher
    ..In some of these mutations, the pathologic consequence is uncertain and needs further investigation. To address this question we propose and use a systematic algorithm to classify the putative pathology of AD mutations. ..
  5. Six E, Ndiaye D, Laabi Y, Brou C, Gupta Rossi N, Israel A, et al. The Notch ligand Delta1 is sequentially cleaved by an ADAM protease and gamma-secretase. Proc Natl Acad Sci U S A. 2003;100:7638-43 pubmed
    ..Therefore Dll1 is a substrate for regulated intramembrane proteolysis, and its intracellular region possibly fulfills a specific function in the nucleus. ..
  6. Scacchi R, Gambina G, Moretto G, Corbo R. A mutation screening by DHPLC of PSEN1 and APP genes reveals no significant variation associated with the sporadic late-onset form of Alzheimer's disease. Neurosci Lett. 2007;418:282-5 pubmed
    ..We concluded that the variation in the screened exons of the APP and PSEN1 genes, reportedly associated with familial AD, is not present in LOAD. ..
  7. Pigino G, Morfini G, Pelsman A, Mattson M, Brady S, Busciglio J. Alzheimer's presenilin 1 mutations impair kinesin-based axonal transport. J Neurosci. 2003;23:4499-508 pubmed
    ..Recent work indicates that presenilin 1 (PS1) interacts with glycogen synthase kinase 3beta (GSK3beta)...
  8. Culvenor J, Ilaya N, Ryan M, Canterford L, Hoke D, Williamson N, et al. Characterization of presenilin complexes from mouse and human brain using Blue Native gel electrophoresis reveals high expression in embryonic brain and minimal change in complex mobility with pathogenic presenilin mutations. Eur J Biochem. 2004;271:375-85 pubmed
    ..Using Blue Native gel electrophoresis (BN/PAGE) we have studied endogenous presenilin 1 complex mass, stability and association with nicastrin, presenilin enhancer-2 and anterior pharynx defective-1...
  9. Kauwe J, Jacquart S, Chakraverty S, Wang J, Mayo K, Fagan A, et al. Extreme cerebrospinal fluid amyloid beta levels identify family with late-onset Alzheimer's disease presenilin 1 mutation. Ann Neurol. 2007;61:446-53 pubmed
    ..Mutations in presenilin 1 (PSEN1) are known to cause AD and change Abeta levels...

More Information

Publications69

  1. He G, Luo W, Li P, Remmers C, Netzer W, Hendrick J, et al. Gamma-secretase activating protein is a therapeutic target for Alzheimer's disease. Nature. 2010;467:95-8 pubmed publisher
    ..Thus, GSAP can serve as an amyloid-beta-lowering therapeutic target without affecting other key functions of gamma-secretase. ..
  2. Watanabe N, Takagi S, Tominaga A, Tomita T, Image Image I, Iwatsubo T, et al. Functional analysis of the transmembrane domains of presenilin 1: participation of transmembrane domains 2 and 6 in the formation of initial substrate-binding site of gamma-secretase. J Biol Chem. 2010;285:19738-46 pubmed publisher
    ..We previously analyzed the functional roles of the N-terminal transmembrane domains (TMDs) 1-6 of PS1 in the assembly and proteolytic activity of the gamma-secretase using a series of TMD-swap PS1 mutants...
  3. Cheung K, Shineman D, Müller M, Cardenas C, Mei L, Yang J, et al. Mechanism of Ca2+ disruption in Alzheimer's disease by presenilin regulation of InsP3 receptor channel gating. Neuron. 2008;58:871-83 pubmed publisher
    ..Here, we demonstrate that FAD mutant PS1 (M146L)and PS2 (N141I) interact with the inositol 1,4,5-trisphosphate receptor (InsP3R) Ca2+ release channel and ..
  4. Nelson O, Tu H, Lei T, Bentahir M, De Strooper B, Bezprozvanny I. Familial Alzheimer disease-linked mutations specifically disrupt Ca2+ leak function of presenilin 1. J Clin Invest. 2007;117:1230-9 pubmed
    ..In addition, a number of mutations in presenilin-1 (PS1) have been suggested to be associated with the occurrence of frontal temporal dementia (FTD)...
  5. Cacquevel M, Aeschbach L, Houacine J, Fraering P. Alzheimer's disease-linked mutations in presenilin-1 result in a drastic loss of activity in purified ?-secretase complexes. PLoS ONE. 2012;7:e35133 pubmed publisher
    ..familial forms of Alzheimer's disease (FAD) are found most frequently in PSEN1, the gene encoding presenilin-1 (PS1)...
  6. Lazarov O, Peterson L, Peterson D, Sisodia S. Expression of a familial Alzheimer's disease-linked presenilin-1 variant enhances perforant pathway lesion-induced neuronal loss in the entorhinal cortex. J Neurosci. 2006;26:429-34 pubmed
    ..familial forms of AD (FAD) are caused by mutations in genes encoding amyloid precursor protein, presenilin-1 (PS1), and presenilin 2...
  7. De Strooper B. Loss-of-function presenilin mutations in Alzheimer disease. Talking Point on the role of presenilin mutations in Alzheimer disease. EMBO Rep. 2007;8:141-6 pubmed
    ..In this review, I evaluate the implications of this model for the amyloid-cascade hypothesis and for the efficacy of presenilin/gamma-secretase as a drug target. ..
  8. Wang R, Wang B, He W, Zheng H. Wild-type presenilin 1 protects against Alzheimer disease mutation-induced amyloid pathology. J Biol Chem. 2006;281:15330-6 pubmed
    Mutations in presenilin 1 (PS1) lead to dominant inheritance of early onset familial Alzheimer disease (FAD)...
  9. Morohashi Y, Kan T, Tominari Y, Fuwa H, Okamura Y, Watanabe N, et al. 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. 2006;281:14670-6 pubmed
    ..transition-state analogue inhibitor L-685,458 or alpha-helical peptidic inhibitor attenuated the photolabeling of PS1 only at higher concentrations...
  10. Silveyra M, Evin G, Montenegro M, Vidal C, Martinez S, Culvenor J, et al. Presenilin 1 interacts with acetylcholinesterase and alters its enzymatic activity and glycosylation. Mol Cell Biol. 2008;28:2908-19 pubmed publisher
    b>Presenilin 1 (PS1) plays a critical role in the gamma-secretase processing of the amyloid precursor protein to generate the beta-amyloid peptide, which accumulates in plaques in the pathogenesis of Alzheimer's disease (AD)...
  11. Bernardi L, Tomaino C, Anfossi M, Gallo M, Geracitano S, Costanzo A, et al. Novel PSEN1 and PGRN mutations in early-onset familial frontotemporal dementia. Neurobiol Aging. 2009;30:1825-33 pubmed publisher
    ..PGRN mutation frequency was low in our sample. The presence of a novel PSEN1 mutation suggests that presenilin molecular studies should be performed when screening for MAPT and PGRN genes is negative. ..
  12. Knappenberger K, Tian G, Ye X, Sobotka Briner C, Ghanekar S, Greenberg B, et al. Mechanism of gamma-secretase cleavage activation: is gamma-secretase regulated through autoinhibition involving the presenilin-1 exon 9 loop?. Biochemistry. 2004;43:6208-18 pubmed
    Maturation of gamma-secretase requires an endoproteolytic cleavage in presenilin-1 (PS1) within a peptide loop encoded by exon 9 of the corresponding gene. Deletion of the loop has been demonstrated to cause familial Alzheimer's disease...
  13. Popescu B, Cedazo Minguez A, Benedikz E, Nishimura T, Winblad B, Ankarcrona M, et al. Gamma-secretase activity of presenilin 1 regulates acetylcholine muscarinic receptor-mediated signal transduction. J Biol Chem. 2004;279:6455-64 pubmed
    Familial Alzheimer's disease (FAD) presenilin 1 (PS1) mutations give enhanced calcium responses upon different stimuli, attenuated capacitative calcium entry, an increased sensitivity of cells to undergo apoptosis, and increased gamma-..
  14. Wahlster L, Arimon M, Nasser Ghodsi N, Post K, Serrano Pozo A, Uemura K, et al. Presenilin-1 adopts pathogenic conformation in normal aging and in sporadic Alzheimer's disease. Acta Neuropathol. 2013;125:187-99 pubmed publisher
    ..While genetic mutations in amyloid precursor protein and presenilin-1 and -2 (PS1 and PS2) genes cause early-onset familial AD, the etiology of sporadic AD is not fully understood...
  15. Acosta Baena N, Sepulveda Falla D, Lopera Gómez C, Jaramillo Elorza M, Moreno S, Aguirre Acevedo D, et al. Pre-dementia clinical stages in presenilin 1 E280A familial early-onset Alzheimer's disease: a retrospective cohort study. Lancet Neurol. 2011;10:213-20 pubmed publisher
    ..We assessed descendants of individuals with a mutation in presenilin 1 (PSEN1) that causes familial AD, with the aim of identifying distinct stages of clinical progression to AD ..
  16. Wang B, Yang W, Wen W, Sun J, Su B, Liu B, et al. Gamma-secretase gene mutations in familial acne inversa. Science. 2010;330:1065 pubmed publisher
  17. Veeraraghavalu K, Choi S, Zhang X, Sisodia S. Presenilin 1 mutants impair the self-renewal and differentiation of adult murine subventricular zone-neuronal progenitors via cell-autonomous mechanisms involving notch signaling. J Neurosci. 2010;30:6903-15 pubmed publisher
    ..While genetic ablation studies have revealed a role for presenilin 1 (PS1) in embryonic neurogenesis, little information has emerged regarding the potential effects of FAD-linked ..
  18. Wolfe M. When loss is gain: reduced presenilin proteolytic function leads to increased Abeta42/Abeta40. Talking Point on the role of presenilin mutations in Alzheimer disease. EMBO Rep. 2007;8:136-40 pubmed
    More than 100 missense mutations in presenilin 1 and 2 are associated with early-onset dominant Alzheimer disease...
  19. Shimojo M, Sahara N, Murayama M, Ichinose H, Takashima A. Decreased Abeta secretion by cells expressing familial Alzheimer's disease-linked mutant presenilin 1. Neurosci Res. 2007;57:446-53 pubmed
    ..Familial Alzheimer's disease (FAD) results from PS mutations, which may alter gamma-secretase activity to enhance the production of highly aggregable ..
  20. Reiman E, Quiroz Y, Fleisher A, Chen K, Velez Pardo C, Jimenez Del Rio M, et al. Brain imaging and fluid biomarker analysis in young adults at genetic risk for autosomal dominant Alzheimer's disease in the presenilin 1 E280A kindred: a case-control study. Lancet Neurol. 2012;11:1048-56 pubmed publisher
    ..Between January and August, 2010, 18-26-year-old presenilin 1 (PSEN1) E280A mutation carriers and non-carriers from the Colombian Alzheimer's Prevention Initiative Registry ..
  21. Fraering P, Ye W, Strub J, Dolios G, LaVoie M, Ostaszewski B, et al. Purification and characterization of the human gamma-secretase complex. Biochemistry. 2004;43:9774-89 pubmed
  22. Lleo A, Berezovska O, Herl L, Raju S, Deng A, Bacskai B, et al. Nonsteroidal anti-inflammatory drugs lower Abeta42 and change presenilin 1 conformation. Nat Med. 2004;10:1065-6 pubmed
    ..energy transfer method, that Abeta(42)-lowering NSAIDs specifically affect the proximity between APP and presenilin 1 and alter presenilin 1 conformation both in vitro and in vivo, suggesting a novel allosteric mechanism of ..
  23. Chyung J, Raper D, Selkoe D. Gamma-secretase exists on the plasma membrane as an intact complex that accepts substrates and effects intramembrane cleavage. J Biol Chem. 2005;280:4383-92 pubmed
  24. Marambaud P, Wen P, Dutt A, Shioi J, Takashima A, Siman R, et al. A CBP binding transcriptional repressor produced by the PS1/epsilon-cleavage of N-cadherin is inhibited by PS1 FAD mutations. Cell. 2003;114:635-45 pubmed
    ..Importantly, PS1 mutations associated with familial AD (FAD) and a gamma-secretase dominant-negative mutation inhibit N-Cad/CTF2 production and upregulate CREB-mediated ..
  25. Borghi R, Piccini A, Barini E, Cirmena G, Guglielmotto M, Tamagno E, et al. Upregulation of presenilin 1 in brains of sporadic, late-onset Alzheimer's disease. J Alzheimers Dis. 2010;22:771-5 pubmed publisher
    ..We evaluated mRNA expression and protein levels of presenilin 1 (PS1) and ?-secretase activity in the frontal cortex of 32 cases with late-onset sporadic AD and those of 29 ..
  26. Area Gomez E, de Groof A, Boldogh I, Bird T, Gibson G, Koehler C, et al. Presenilins are enriched in endoplasmic reticulum membranes associated with mitochondria. Am J Pathol. 2009;175:1810-6 pubmed publisher
    Presenilin-1 (PS1) and -2 (PS2), which when mutated cause familial Alzheimer disease, have been localized to numerous compartments of the cell, including the endoplasmic reticulum, Golgi, nuclear envelope, endosomes, lysosomes, the ..
  27. Placanica L, Tarassishin L, Yang G, Peethumnongsin E, Kim S, Zheng H, et al. Pen2 and presenilin-1 modulate the dynamic equilibrium of presenilin-1 and presenilin-2 gamma-secretase complexes. J Biol Chem. 2009;284:2967-77 pubmed publisher
    ..We show that our in vitro assay system recapitulates the effect of PS1 mutations on the Abeta42:Abeta40 ratio observed in cell and animal models...
  28. Takeo K, Watanabe N, Tomita T, Iwatsubo T. Contribution of the ?-secretase subunits to the formation of catalytic pore of presenilin 1 protein. J Biol Chem. 2012;287:25834-43 pubmed publisher
    ..We propose a model in which the ?-secretase subunits restrict the arrangement of the transmembrane domains of PS during the formation of the functional structure of the catalytic pore. ..
  29. Laudon H, Hansson E, Melén K, Bergman A, Farmery M, Winblad B, et al. A nine-transmembrane domain topology for presenilin 1. J Biol Chem. 2005;280:35352-60 pubmed
    ..used a more subtle N-linked glycosylation scanning approach, which allowed us to assess the topology of functional PS1 molecules...
  30. Watanabe N, Tomita T, Sato C, Kitamura T, Morohashi Y, Iwatsubo T. Pen-2 is incorporated into the gamma-secretase complex through binding to transmembrane domain 4 of presenilin 1. J Biol Chem. 2005;280:41967-75 pubmed
    ..We reconstituted PS1 in Psen1/Psen2 deficient cells by expressing a series of PS1 mutants in which one of the N-terminal six ..
  31. Saura C, Servián Morilla E, Scholl F. Presenilin/?-secretase regulates neurexin processing at synapses. PLoS ONE. 2011;6:e19430 pubmed publisher
    ..Interestingly, presenilin 1 (PS1) is recruited to glutamatergic terminals mediated by neuroligin-1, thus concentrating PS1 at terminals ..
  32. Chen F, Hasegawa H, Schmitt Ulms G, Kawarai T, Bohm C, Katayama T, et al. TMP21 is a presenilin complex component that modulates gamma-secretase but not epsilon-secretase activity. Nature. 2006;440:1208-12 pubmed
    The presenilin proteins (PS1 and PS2) and their interacting partners nicastrin, aph-1 (refs 4, 5) and pen-2 (ref...
  33. Spasic D, Tolia A, Dillen K, Baert V, De Strooper B, Vrijens S, et al. Presenilin-1 maintains a nine-transmembrane topology throughout the secretory pathway. J Biol Chem. 2006;281:26569-77 pubmed
    ..We revisited presenilin-1 topology by inserting glycosylation consensus sequences in human PS1 and expressing the obtained mutants in a presenilin-1 and 2 knock-out background...
  34. Balasa M, Vidal Piñeiro D, Lladó A, Antonell A, Bosch B, Castellanos F, et al. PSEN1 mutation carriers present lower cerebrospinal fluid amyoid-?42 levels than sporadic early-onset Alzheimer's disease patients but no differences in neuronal injury biomarkers. J Alzheimers Dis. 2012;30:605-16 pubmed publisher
    ..The lack of significant differences in relation to t-tau and p-tau levels and to the severity of CTh or grey matter loss suggests a similar level of neuronal injury despite higher A?(42) load in PSEN1. ..
  35. Okochi M, Tagami S, Yanagida K, Takami M, Kodama T, Mori K, et al. ?-secretase modulators and presenilin 1 mutants act differently on presenilin/?-secretase function to cleave A?42 and A?43. Cell Rep. 2013;3:42-51 pubmed publisher
    ..of PS/?-secretase-bound A?42 (increase k(cat)) and slow its dissociation from the enzyme (decrease k(b)), whereas PS1 mutants and inverse GSMs show the opposite effects...
  36. Gerrish A, Russo G, Richards A, Moskvina V, Ivanov D, Harold D, et al. The role of variation at AβPP, PSEN1, PSEN2, and MAPT in late onset Alzheimer's disease. J Alzheimers Dis. 2012;28:377-87 pubmed publisher
    ..However, the gene-wide effect observed at MAPT indicates a possible contribution to disease risk which requires further study. ..
  37. Benítez B, Karch C, Cai Y, Jin S, Cooper B, Carrell D, et al. The PSEN1, p.E318G variant increases the risk of Alzheimer's disease in APOE-ε4 carriers. PLoS Genet. 2013;9:e1003685 pubmed publisher
    ..We demonstrate that the effect of PSEN1, p.E318G on AD susceptibility is largely dependent on an interaction with APOE-ε4 and mediated by an increased burden of Aβ deposition. ..
  38. Chávez Gutiérrez L, Bammens L, Benilova I, Vandersteen A, Benurwar M, Borgers M, et al. The mechanism of ?-Secretase dysfunction in familial Alzheimer disease. EMBO J. 2012;31:2261-74 pubmed publisher
    ..mutations in the presenilins (PSEN) or the amyloid precursor protein (APP) genes cause familial Alzheimer disease (FAD) are controversial...
  39. Cruchaga C, Haller G, Chakraverty S, Mayo K, Vallania F, Mitra R, et al. Rare variants in APP, PSEN1 and PSEN2 increase risk for AD in late-onset Alzheimer's disease families. PLoS ONE. 2012;7:e31039 pubmed publisher
    ..This study clearly demonstrates that rare variants in these genes could explain an important proportion of genetic heritability of AD, which is not detected by GWAS. ..
  40. Hébert S, Godin C, Levesque G. Oligomerization of human presenilin-1 fragments. FEBS Lett. 2003;550:30-4 pubmed
    To gain insight into presenilin-1 (PS1) structural aspects, we explored the structure-function relationship of its N- and C-terminal (NTF and CTF, respectively) complexes...
  41. Hébert S, Serneels L, Dejaegere T, Horré K, Dabrowski M, Baert V, et al. Coordinated and widespread expression of gamma-secretase in vivo: evidence for size and molecular heterogeneity. Neurobiol Dis. 2004;17:260-72 pubmed
    ..In conclusion, our results suggest that gamma-secretase is a heterogeneous family of protein complexes widely expressed in the adult organism. ..
  42. Zatti G, Burgo A, Giacomello M, Barbiero L, Ghidoni R, Sinigaglia G, et al. Presenilin mutations linked to familial Alzheimer's disease reduce endoplasmic reticulum and Golgi apparatus calcium levels. Cell Calcium. 2006;39:539-50 pubmed
    Presenilin-1 and -2 (PS1 and PS2) mutations, the major cause of familial Alzheimer's disease (FAD), have been causally implicated in the pathogenesis of neuronal cell death through a perturbation of cellular Ca(2+) homeostasis...
  43. Dumanchin C, Tournier I, Martin C, Didic M, Belliard S, Carlander B, et al. Biological effects of four PSEN1 gene mutations causing Alzheimer disease with spastic paraparesis and cotton wool plaques. Hum Mutat. 2006;27:1063 pubmed
    ..We conclude that none of the previously proposed mechanisms, i.e. exceptionally large increases in secreted Abeta42 levels or loss of PSEN1 exons 8 or 9, provides complete explanation of the CWP/SP phenotype...
  44. Tu H, Nelson O, Bezprozvanny A, Wang Z, Lee S, Hao Y, et al. Presenilins form ER Ca2+ leak channels, a function disrupted by familial Alzheimer's disease-linked mutations. Cell. 2006;126:981-93 pubmed
    ..Mutations in presenilins 1 and 2 (PS1 and PS2) account for approximately 40% of familial AD (FAD) cases...
  45. Lee J, Yu W, Kumar A, Lee S, Mohan P, Peterhoff C, et al. Lysosomal proteolysis and autophagy require presenilin 1 and are disrupted by Alzheimer-related PS1 mutations. Cell. 2010;141:1146-58 pubmed publisher
    ..Here, we show that macroautophagy requires the Alzheimer's disease (AD)-related protein presenilin-1 (PS1)...
  46. Cohen R, Rezai Zadeh K, Weitz T, Rentsendorj A, Gate D, Spivak I, et al. A transgenic Alzheimer rat with plaques, tau pathology, behavioral impairment, oligomeric a?, and frank neuronal loss. J Neurosci. 2013;33:6245-56 pubmed publisher
    ..We have developed a Tg rat model (line TgF344-AD) expressing mutant human amyloid precursor protein (APPsw) and presenilin 1 (PS1?E9) genes, each independent causes of early-onset familial AD...
  47. Nyabi O, Bentahir M, Horré K, Herreman A, Gottardi Littell N, Van Broeckhoven C, et al. Presenilins mutated at Asp-257 or Asp-385 restore Pen-2 expression and Nicastrin glycosylation but remain catalytically inactive in the absence of wild type Presenilin. J Biol Chem. 2003;278:43430-6 pubmed
  48. Dowjat W, Kuchna I, Wisniewski T, Wegiel J. A novel highly pathogenic Alzheimer presenilin-1 mutation in codon 117 (Pro117Ser): Comparison of clinical, neuropathological and cell culture phenotypes of Pro117Leu and Pro117Ser mutations. J Alzheimers Dis. 2004;6:31-43 pubmed
    A novel presenilin-1 (PS1) mutation (P117S) in an American pedigree is described...
  49. Albani D, Roiter I, Artuso V, Batelli S, Prato F, Pesaresi M, et al. Presenilin-1 mutation E318G and familial Alzheimer's disease in the Italian population. Neurobiol Aging. 2007;28:1682-8 pubmed
    ..Nevertheless, this mutation was reported to be a genetic risk factor for familial Alzheimer's disease (FAD) in the Australian population...
  50. Sato C, Morohashi Y, Tomita T, Iwatsubo T. Structure of the catalytic pore of gamma-secretase probed by the accessibility of substituted cysteines. J Neurosci. 2006;26:12081-8 pubmed
    ..Collectively, our data suggest that the active site of gamma-secretase resides in a catalytic pore filled with water within the lipid bilayer and is tapered around the catalytic aspartates. ..
  51. Quintero Monzon O, Martin M, Fernandez M, Cappello C, Krzysiak A, Osenkowski P, et al. Dissociation between the processivity and total activity of ?-secretase: implications for the mechanism of Alzheimer's disease-causing presenilin mutations. Biochemistry. 2011;50:9023-35 pubmed publisher
    ..Factors that control initial proteolysis of APP at the ? site apparently differ significantly from factors affecting subsequent trimming and the distribution of A? peptides. ..
  52. Knight W, Kennedy J, Mead S, Rossor M, Beck J, Collinge J, et al. A novel presenilin 1 deletion (p.L166del) associated with early onset familial Alzheimer's disease. Eur J Neurol. 2007;14:829-31 pubmed
    ..Analysis of the presenilin 1 gene (PSEN1) revealed a 496_498delCTT mutation at codon 166...
  53. Page R, Baumann K, Tomioka M, Pérez Revuelta B, Fukumori A, Jacobsen H, et al. Generation of Abeta38 and Abeta42 is independently and differentially affected by familial Alzheimer disease-associated presenilin mutations and gamma-secretase modulation. J Biol Chem. 2008;283:677-83 pubmed
    ..The amount of Abeta(42) produced by cells expressing 10 different familial Alzheimer disease (FAD)-associated mutations in presenilin (PS) 1, the catalytic subunit of gamma-secretase, appeared to correlate with ..
  54. Uemura K, Lill C, Li X, Peters J, Ivanov A, Fan Z, et al. Allosteric modulation of PS1/gamma-secretase conformation correlates with amyloid beta(42/40) ratio. PLoS ONE. 2009;4:e7893 pubmed publisher
    b>Presenilin 1(PS1) is the catalytic subunit of gamma-secretase, the enzyme responsible for the Abeta C-terminal cleavage site, which results in the production of Abeta peptides of various lengths...
  55. Heilig E, Xia W, Shen J, Kelleher R. A presenilin-1 mutation identified in familial Alzheimer disease with cotton wool plaques causes a nearly complete loss of gamma-secretase activity. J Biol Chem. 2010;285:22350-9 pubmed publisher
    Mutations in presenilin-1 and presenilin-2 (PS1 and PS2) are the most common cause of familial Alzheimer disease...
  56. Silveyra M, García Ayllón M, Serra Basante C, Mazzoni V, García Gutiérrez M, Manzanares J, et al. Changes in acetylcholinesterase expression are associated with altered presenilin-1 levels. Neurobiol Aging. 2012;33:627.e27-37 pubmed publisher
    We have previously identified presenilin-1 (PS1), the active component of the ?-secretase complex, as an interacting protein of the amyloid-associated enzyme acetylcholinesterase (AChE)...
  57. Sato T, Diehl T, Narayanan S, Funamoto S, Ihara Y, De Strooper B, et al. Active gamma-secretase complexes contain only one of each component. J Biol Chem. 2007;282:33985-93 pubmed
    ..Taken together, these results demonstrate that the stoichiometry of gamma-components presenilin:Pen-2:nicastrin:Aph-1 is 1:1:1:1. ..
  58. Lladó A, Fortea J, Ojea T, Bosch B, Sanz P, Valls Sole J, et al. A novel PSEN1 mutation (K239N) associated with Alzheimer's disease with wide range age of onset and slow progression. Eur J Neurol. 2010;17:994-6 pubmed publisher
    ..The K239N mutation is associated with autosomal dominant AD with a wide range of age of onset and incomplete penetrance at the age of 65, prominent behavioural features and slow progression. ..
  59. Veeraraghavalu K, Sisodia S. Mutant presenilin 1 expression in excitatory neurons impairs enrichment-mediated phenotypes of adult hippocampal progenitor cells. Proc Natl Acad Sci U S A. 2013;110:9148-53 pubmed publisher
    Inheritance of mutant presenilin 1 genes (PSEN1) encoding presenilin 1 (PS1)variants causes autosomal dominant forms of familial Alzheimer's disease (FAD)...
  60. Beher D, Fricker M, Nadin A, Clarke E, Wrigley J, Li Y, et al. In vitro characterization of the presenilin-dependent gamma-secretase complex using a novel affinity ligand. Biochemistry. 2003;42:8133-42 pubmed
    ..This was also reflected by a co-distribution of both enzyme activities in subcellular fractions enriched for trans-Golgi network membranes. ..