Genomes and Genes
Gene Symbol: presenilin 1
Description: presenilin 1
Alias: Ad3h, PS-1, PS1, S182, presenilin-1
Products: presenilin 1
- Yagi T, Giallourakis C, Mohanty S, Scheidig C, Shen J, Zheng H, et al. Defective signal transduction in B lymphocytes lacking presenilin proteins. Proc Natl Acad Sci U S A. 2008;105:979-84 pubmed publisher..To test these computational predictions, we analyzed mice carrying a conditional allele of PS1 and a germ line-inactivating allele of PS2, together with Cre site-specific recombinase expression under the ..
- Howlett D, Bowler K, Soden P, Riddell D, Davis J, Richardson J, et al. Abeta deposition and related pathology in an APP x PS1 transgenic mouse model of Alzheimer's disease. Histol Histopathol. 2008;23:67-76 pubmed publisher..TASTPM mice, therefore, exhibit a number of the pathological characteristics of disease progression in AD and may provide a means for assessment of novel therapeutic agents directed towards modifying or halting disease progression. ..
- Clinton L, Billings L, Green K, Caccamo A, Ngo J, Oddo S, et al. Age-dependent sexual dimorphism in cognition and stress response in the 3xTg-AD mice. Neurobiol Dis. 2007;28:76-82 pubmed..Thus, the enhanced corticosterone response of the young female mice likely underlies their poorer performance on stressful tasks. ..
- Halagappa V, Guo Z, Pearson M, Matsuoka Y, Cutler R, LaFerla F, et al. Intermittent fasting and caloric restriction ameliorate age-related behavioral deficits in the triple-transgenic mouse model of Alzheimer's disease. Neurobiol Dis. 2007;26:212-20 pubmed..We conclude that CR and IF dietary regimens can ameliorate age-related deficits in cognitive function by mechanisms that may or may not be related to Abeta and tau pathologies. ..
- 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...
- 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 publisherb>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...
- Li T, Wen H, Brayton C, Laird F, Ma G, Peng S, et al. Moderate reduction of gamma-secretase attenuates amyloid burden and limits mechanism-based liabilities. J Neurosci. 2007;27:10849-59 pubmed..Our findings suggest that moderate inhibition of gamma-secretase represents an attractive anti-amyloid therapy for Alzheimer's disease. ..
- Zou K, Hosono T, Nakamura T, Shiraishi H, Maeda T, Komano H, et al. Novel role of presenilins in maturation and transport of integrin beta 1. Biochemistry. 2008;47:3370-8 pubmed publisher..By characterizing PS-deficient fibroblasts, we found that integrin beta1 maturation is promoted markedly in PS1 and PS2 double-deficient fibroblasts and moderately in PS1- or PS2-deficient fibroblasts; in contrast, nicastrin ..
- Fonseca M, Ager R, Chu S, Yazan O, Sanderson S, LaFerla F, et al. Treatment with a C5aR antagonist decreases pathology and enhances behavioral performance in murine models of Alzheimer's disease. J Immunol. 2009;183:1375-83 pubmed publisher..e., C5aR) can interfere with neuroinflammation and neurodegeneration in AD rodent models, suggesting a novel therapeutic target for reducing pathology and improving cognitive function in human AD patients. ..
- Fukumori A, Fluhrer R, Steiner H, Haass C. Three-amino acid spacing of presenilin endoproteolysis suggests a general stepwise cleavage of gamma-secretase-mediated intramembrane proteolysis. J Neurosci. 2010;30:7853-62 pubmed publisherPresenilin (PS1 or PS2) is the catalytic component of the gamma-secretase complex, which mediates the final proteolytic processing step leading to the Alzheimer's disease (AD)-characterizing amyloid beta-peptide...
- Knight E, Brown T, Gumusgoz S, Smith J, Waters E, Allan S, et al. Age-related changes in core body temperature and activity in triple-transgenic Alzheimer's disease (3xTgAD) mice. Dis Model Mech. 2013;6:160-70 pubmed publisher..The 3xTgAD mouse might therefore be an appropriate model for studying the underlying mechanisms involved in non-cognitive behavioural changes in AD. ..
- Filali M, Lalonde R, Theriault P, Julien C, Calon F, Planel E. Cognitive and non-cognitive behaviors in the triple transgenic mouse model of Alzheimer's disease expressing mutated APP, PS1, and Mapt (3xTg-AD). Behav Brain Res. 2012;234:334-42 pubmed publisher..On the contrary, the mutants did not differ from controls in pain thresholds, nest-building, and various reflexes determined by the SHIRPA primary screen and were even better on the rotorod test of motor coordination. ..
- Adebakin A, Bradley J, Gumusgoz S, Waters E, Lawrence C. Impaired satiation and increased feeding behaviour in the triple-transgenic Alzheimer's disease mouse model. PLoS ONE. 2012;7:e45179 pubmed publisher..These data demonstrate that 3×TgAD mice show increased feeding behaviour and insensitivity to satiation, which is possibly due to defective gut-brain signalling in response to endogenous satiety factors released by food ingestion. ..
- Zhang H, Sun S, Herreman A, De Strooper B, Bezprozvanny I. Role of presenilins in neuronal calcium homeostasis. J Neurosci. 2010;30:8566-80 pubmed publisher..of Ca(2+) imaging experiments with primary neuronal cultures from conditional presenilin double-knock-out mice (PS1(dTAG/dTAG), PS2(-/-)) and from triple-transgenic AD mice (KI-PS1(M146V), Thy1-APP(KM670/671NL), Thy1-tau(P301L))...
- Chakroborty S, Goussakov I, Miller M, Stutzmann G. Deviant ryanodine receptor-mediated calcium release resets synaptic homeostasis in presymptomatic 3xTg-AD mice. J Neurosci. 2009;29:9458-70 pubmed publisher..These early signaling alterations may underlie the later synaptic breakdown and cognitive deficits characteristic of later stage AD. ..
- Banaceur S, Banasr S, Sakly M, Abdelmelek H. Whole body exposure to 2.4 GHz WIFI signals: effects on cognitive impairment in adult triple transgenic mouse models of Alzheimer's disease (3xTg-AD). Behav Brain Res. 2013;240:197-201 pubmed publisher..Our data demonstrate for the first time that RF improves cognitive behavior of 3xTg-AD mice. We conclude that RF exposure may represent an effective memory-enhancing approach in Alzheimer's disease. ..
- Cheung K, Mei L, Mak D, Hayashi I, Iwatsubo T, Kang D, et al. Gain-of-function enhancement of IP3 receptor modal gating by familial Alzheimer's disease-linked presenilin mutants in human cells and mouse neurons. Sci Signal. 2010;3:ra22 pubmed publisherFamilial Alzheimer's disease (FAD) is caused by mutations in amyloid precursor protein or presenilins (PS1 and PS2)...
- Neely K, Green K, LaFerla F. Presenilin is necessary for efficient proteolysis through the autophagy-lysosome system in a ?-secretase-independent manner. J Neurosci. 2011;31:2781-91 pubmed publisher..The role of presenilins in autophagy has many implications for its function in neurological diseases such as AD. ..
- Zhang X, Garbett K, Veeraraghavalu K, Wilburn B, Gilmore R, Mirnics K, et al. A role for presenilins in autophagy revisited: normal acidification of lysosomes in cells lacking PSEN1 and PSEN2. J Neurosci. 2012;32:8633-48 pubmed publisherPresenilins 1 and 2 (PS1 and PS2) are the catalytic subunits of the ?-secretase complex, and genes encoding mutant PS1 and PS2 variants cause familial forms of Alzheimer's disease. Lee et al...
- Zhang Y, Kurup P, Xu J, Carty N, Fernandez S, Nygaard H, et al. Genetic reduction of striatal-enriched tyrosine phosphatase (STEP) reverses cognitive and cellular deficits in an Alzheimer's disease mouse model. Proc Natl Acad Sci U S A. 2010;107:19014-9 pubmed publisher..Our results suggest that STEP inhibitors may prove therapeutic for this devastating disorder. ..
- Marques S, Lemos R, Ferreiro E, Martins M, de Mendonca A, Santana I, et al. Epigenetic regulation of BACE1 in Alzheimer's disease patients and in transgenic mice. Neuroscience. 2012;220:256-66 pubmed publisher..Overall, our results suggest that chromatin remodeling plays a role in mRNA alterations in AD, prompting for broader and more detailed studies of chromatin and other epigenetic alterations and their potential use as biomarkers in AD. ..
- Ong C, Sedy J, Murphy K, Kopan R. Notch and presenilin regulate cellular expansion and cytokine secretion but cannot instruct Th1/Th2 fate acquisition. PLoS ONE. 2008;3:e2823 pubmed publisher..The controversies surrounding the role of Notch and presenilins in Th1/Th2 polarization may reflect their role as genetic modifiers of T-helper cells differentiation. ..
- Ferjentsik Z, Hayashi S, Dale J, Bessho Y, Herreman A, De Strooper B, et al. Notch is a critical component of the mouse somitogenesis oscillator and is essential for the formation of the somites. PLoS Genet. 2009;5:e1000662 pubmed publisher..We propose that, at least in the mouse embryo, Notch activity is absolutely essential for the formation of a segmented body axis...
- Han W, Ji T, Wang L, Yan L, Wang H, Luo Z, et al. Abnormalities in periodontal and salivary tissues in conditional presenilin 1 and presenilin 2 double knockout mice. Mol Cell Biochem. 2011;347:13-20 pubmed publisherWe used forebrain-specific conditional presenilin 1 (PS1) and presenilin 2 (PS2) double knockout mice (dKO mice), which exhibit neurodegenerative disease-like symptoms, including inflammation of the brain and periphery, to investigate ..
- Hilton M, Tu X, Wu X, Bai S, Zhao H, Kobayashi T, et al. Notch signaling maintains bone marrow mesenchymal progenitors by suppressing osteoblast differentiation. Nat Med. 2008;14:306-14 pubmed publisher..Thus, mesenchymal progenitors may be expanded in vitro by activating the Notch pathway, whereas bone formation in vivo may be enhanced by transiently suppressing this pathway. ..
- Lazarov O, Morfini G, Pigino G, Gadadhar A, Chen X, Robinson J, et al. Impairments in fast axonal transport and motor neuron deficits in transgenic mice expressing familial Alzheimer's disease-linked mutant presenilin 1. J Neurosci. 2007;27:7011-20 pubmed..Expression of mutant PS1 variants causes familial forms of Alzheimer's disease (FAD)...
- Dolev I, Fogel H, Milshtein H, Berdichevsky Y, Lipstein N, Brose N, et al. Spike bursts increase amyloid-? 40/42 ratio by inducing a presenilin-1 conformational change. Nat Neurosci. 2013;16:587-95 pubmed publisher..Spike bursts boosted A?40/42 through a conformational change in presenilin1 (PS1), the catalytic subunit of ?-secretase, and subsequent increase in A?40 production...
- 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 publisherMutations in presenilin-1 and presenilin-2 (PS1 and PS2) are the most common cause of familial Alzheimer disease...
- 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)...
- Tseng B, Green K, Chan J, Blurton Jones M, LaFerla F. Abeta inhibits the proteasome and enhances amyloid and tau accumulation. Neurobiol Aging. 2008;29:1607-18 pubmed..These findings provide further evidence that the proteasome represents a viable target for therapeutic intervention in AD. ..
- Li H, Wang Z, Wang B, Guo Q, Dolios G, Tabuchi K, et al. Genetic dissection of the amyloid precursor protein in developmental function and amyloid pathogenesis. J Biol Chem. 2010;285:30598-605 pubmed publisher..Our results establish an essential function of the conserved APP intracellular domain in developmental regulation, and this activity can be genetically uncoupled from APP processing and A? pathogenesis. ..
- Maraver A, Tadokoro C, Badura M, Shen J, Serrano M, Lafaille J. Effect of presenilins in the apoptosis of thymocytes and homeostasis of CD8+ T cells. Blood. 2007;110:3218-25 pubmed..T-cell-specific elimination of gamma-secretase was carried out by crossing presenilin-1 (PS1) floxed mice with CD4-Cre mice and PS2 KO mice, generating PS KO mice...
- Sterniczuk R, Antle M, LaFerla F, Dyck R. Characterization of the 3xTg-AD mouse model of Alzheimer's disease: part 2. Behavioral and cognitive changes. Brain Res. 2010;1348:149-55 pubmed publisher..No differences were observed in muscle strength and visuo-motor coordination. Understanding the behavioral manifestations that occur in this model of AD may aid in the early diagnosis and appropriate treatment of AD symptomology. ..
- Müller M, Cardenas C, Mei L, Cheung K, Foskett J. Constitutive cAMP response element binding protein (CREB) activation by Alzheimer's disease presenilin-driven inositol trisphosphate receptor (InsP3R) Ca2+ signaling. Proc Natl Acad Sci U S A. 2011;108:13293-8 pubmed publisher..nitric oxide synthase and c-fos, were enhanced in brains of M146V-KI and 3xTg-AD mice expressing FAD mutant PS1 knocked into the mouse locus...
- Resende R, Moreira P, Proença T, Deshpande A, Busciglio J, Pereira C, et al. Brain oxidative stress in a triple-transgenic mouse model of Alzheimer disease. Free Radic Biol Med. 2008;44:2051-7 pubmed publisher..These alterations are evident during the Abeta oligomerization period, before the appearance of Abeta plaques and neurofibrillary tangles, supporting the view that oxidative stress occurs early in the development of the disease. ..
- Elzinga B, Twomey C, Powell J, Harte F, McCarthy J. Interleukin-1 receptor type 1 is a substrate for gamma-secretase-dependent regulated intramembrane proteolysis. J Biol Chem. 2009;284:1394-409 pubmed publisher..of presenilin-1 residues Pro-374 and Glu-376 by site-directed mutagenesis greatly reduces the ability of PS1 to associate with TRAF6...
- Guo Q, Li H, Gaddam S, Justice N, Robertson C, Zheng H. Amyloid precursor protein revisited: neuron-specific expression and highly stable nature of soluble derivatives. J Biol Chem. 2012;287:2437-45 pubmed publisher..Our results clarify several key questions with regard to the fundamental properties of APP and offer critical cellular insights into the pathophysiology of APP. ..
- Orr M, Salinas A, Buffenstein R, Oddo S. Mammalian target of rapamycin hyperactivity mediates the detrimental effects of a high sucrose diet on Alzheimer's disease pathology. Neurobiol Aging. 2014;35:1233-42 pubmed publisher..Therefore, early interventions to modulate mTOR activity in individuals at high risk of developing diabetes may decrease their AD susceptibility. ..
- Takagi S, Tominaga A, Sato C, Tomita T, Iwatsubo T. Participation of transmembrane domain 1 of presenilin 1 in the catalytic pore structure of the ?-secretase. J Neurosci. 2010;30:15943-50 pubmed publisher..pore" structure of ?-secretase is formed by the transmembrane domains (TMDs) 6, 7, and 9 of presenilin 1 (PS1), the catalytic subunit of ?-secretase, within the membrane...
- Sterniczuk R, Dyck R, LaFerla F, Antle M. Characterization of the 3xTg-AD mouse model of Alzheimer's disease: part 1. Circadian changes. Brain Res. 2010;1348:139-48 pubmed publisher..This study demonstrates that abnormalities in circadian rhythmicity in 3xTg-AD mice precede expected AD pathology. This suggests that human studies may wish to determine if similar circadian dysfunction is predictive of early-onset AD. ..
- Cotel M, Jawhar S, Christensen D, Bayer T, Wirths O. Environmental enrichment fails to rescue working memory deficits, neuron loss, and neurogenesis in APP/PS1KI mice. Neurobiol Aging. 2012;33:96-107 pubmed publisher..Therefore our data might suggest that physical activity and enriched environment might be more beneficial in patients with mild cognitive impairment than in patients with incipient AD. ..
- Phivilay A, Julien C, Tremblay C, Berthiaume L, Julien P, Giguère Y, et al. High dietary consumption of trans fatty acids decreases brain docosahexaenoic acid but does not alter amyloid-beta and tau pathologies in the 3xTg-AD model of Alzheimer's disease. Neuroscience. 2009;159:296-307 pubmed publisher..In summary, TFA intake modulated brain fatty acid profiles but had no significant effect on major brain neuropathological hallmarks of AD in an animal model. ..
- Arsenault D, Julien C, Tremblay C, Calon F. DHA improves cognition and prevents dysfunction of entorhinal cortex neurons in 3xTg-AD mice. PLoS ONE. 2011;6:e17397 pubmed publisher..Our results indicate that cognitive performance and basic physiology of EC neurons depend on DHA intake in a mouse model of AD. ..
- Goussakov I, Miller M, Stutzmann G. NMDA-mediated Ca(2+) influx drives aberrant ryanodine receptor activation in dendrites of young Alzheimer's disease mice. J Neurosci. 2010;30:12128-37 pubmed publisher..We propose that presenilin-linked disruptions in RyR signaling and subsequent CICR via NMDAR-mediated calcium influx alters synaptic function and serves as an early pathogenic factor in AD...
- Torres Lista V, Gimenez Llort L. Impairment of nesting behaviour in 3xTg-AD mice. Behav Brain Res. 2013;247:153-7 pubmed publisher..The reported impairment of nesting behaviour in 3xTg-AD provides another behavioral tool to assess the benefits of preventive and/or therapeutic strategies, as well as the potential action of risk factors of AD, in this animal model. ..
- Clinton L, Blurton Jones M, Myczek K, Trojanowski J, LaFerla F. Synergistic Interactions between Abeta, tau, and alpha-synuclein: acceleration of neuropathology and cognitive decline. J Neurosci. 2010;30:7281-9 pubmed publisher..Together, our data support the notion that Abeta, tau, and alpha-synuclein interact in vivo to promote the aggregation and accumulation of each other and accelerate cognitive dysfunction. ..
- Hirata Fukae C, Li H, HOE H, Gray A, Minami S, Hamada K, et al. Females exhibit more extensive amyloid, but not tau, pathology in an Alzheimer transgenic model. Brain Res. 2008;1216:92-103 pubmed publisher..These findings confirm progressive Abeta pathology in 3xTg-AD transgenic mice, and provide guidance for their use in therapeutic research. ..
- Chávez Gutiérrez L, Tolia A, Maes E, Li T, Wong P, De Strooper B. Glu(332) in the Nicastrin ectodomain is essential for gamma-secretase complex maturation but not for its activity. J Biol Chem. 2008;283:20096-105 pubmed publisher..Consequently, these studies indicate that the main role of the Glu(332) is in the maturation and assembly of gamma-secretase rather than in the recognition of the substrates. ..
- Filali M, Lalonde R, Rivest S. Cognitive and non-cognitive behaviors in an APPswe/PS1 bigenic model of Alzheimer's disease. Genes Brain Behav. 2009;8:143-8 pubmed publisher..In the present study, APPswe/PS1 bigenic mice had higher levels of irritability than non-transgenic controls as measured in the touch escape test...
- Dong S, Li C, Wu P, Tsien J, Hu Y. Environment enrichment rescues the neurodegenerative phenotypes in presenilins-deficient mice. Eur J Neurosci. 2007;26:101-12 pubmed..Furthermore, the beneficial effects of EE may be associated with the inhibition of the expression of immunity and inflammation-related genes in the brain. ..
- 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 ..
- Yao J, Irwin R, Zhao L, Nilsen J, Hamilton R, Brinton R. Mitochondrial bioenergetic deficit precedes Alzheimer's pathology in female mouse model of Alzheimer's disease. Proc Natl Acad Sci U S A. 2009;106:14670-5 pubmed publisher..Mitochondrial dysfunction provides a plausible mechanistic rationale for the hypometabolism in brain that precedes AD diagnosis and suggests therapeutic targets for prevention of AD. ..
- Chadwick W, Mitchell N, Caroll J, Zhou Y, Park S, Wang L, et al. Amitriptyline-mediated cognitive enhancement in aged 3×Tg Alzheimer's disease mice is associated with neurogenesis and neurotrophic activity. PLoS ONE. 2011;6:e21660 pubmed publisher..These results indicate that amitriptyline has significant beneficial actions in aged and damaged AD brains and that it shows promise as a tolerable novel therapeutic for the treatment of AD. ..
- Saito T, Suemoto T, Brouwers N, Sleegers K, Funamoto S, Mihira N, et al. Potent amyloidogenicity and pathogenicity of A?43. Nat Neurosci. 2011;14:1023-32 pubmed publisher..These findings indicate that A?43, an overlooked species, is potently amyloidogenic, neurotoxic and abundant in vivo. ..
- Blurton Jones M, Kitazawa M, Martinez Coria H, Castello N, Muller F, Loring J, et al. Neural stem cells improve cognition via BDNF in a transgenic model of Alzheimer disease. Proc Natl Acad Sci U S A. 2009;106:13594-9 pubmed publisher..Taken together, our findings demonstrate that neural stem cells can ameliorate complex behavioral deficits associated with widespread Alzheimer disease pathology via BDNF. ..
- Guo Q, Zheng H, Justice N. Central CRF system perturbation in an Alzheimer's disease knockin mouse model. Neurobiol Aging. 2012;33:2678-91 pubmed publisher..mouse model of AD that expresses familial AD (FAD) mutations of both APP with humanized amyloid beta (hA?), and presenilin 1 (PS1), in their endogenous patterns (APP/hA?/PS1 animals), corticotropin releasing factor (CRF) levels are ..
- Wang Y, Greig N, Yu Q, Mattson M. Presenilin-1 mutation impairs cholinergic modulation of synaptic plasticity and suppresses NMDA currents in hippocampus slices. Neurobiol Aging. 2009;30:1061-8 pubmedPresenilin-1 (PS1) mutations cause many cases of early-onset inherited Alzheimer's disease, in part, by increasing the production of neurotoxic forms of amyloid beta-peptide (Abeta)...
- Davis K, Eacott M, Easton A, Gigg J. Episodic-like memory is sensitive to both Alzheimer's-like pathological accumulation and normal ageing processes in mice. Behav Brain Res. 2013;254:73-82 pubmed publisher..These results, in combination with our previous findings, support an age-related decline in WWWhich episodic-like memory in mice. Furthermore, this decline is accelerated in the 3xTgAD model. ..
- Ding F, Yao J, Zhao L, Mao Z, Chen S, Brinton R. Ovariectomy induces a shift in fuel availability and metabolism in the hippocampus of the female transgenic model of familial Alzheimer's. PLoS ONE. 2013;8:e59825 pubmed publisher..These findings also indicate that estrogen plays a critical role in sustaining brain bioenergetic capacity through preservation of glucose metabolism. ..
- Nelson O, Supnet C, Tolia A, Horré K, De Strooper B, Bezprozvanny I. Mutagenesis mapping of the presenilin 1 calcium leak conductance pore. J Biol Chem. 2011;286:22339-47 pubmed publisherMissense mutations in presenilin 1 (PS1) and presenilin 2 (PS2) proteins are a major cause of familial Alzheimer disease...