|
ORF cDNA clones
|
CRISPR / TALEN
|
Lentivirus
|
AAV
|
TALE-TF
|
ORF knockin clones
|
|
Antibody
|
Proteins
|
miRNA target clones
|
qPCR primers
|
shRNA clones
|
miRNA products
|
Promoter clones
|
Validated All-in-One™ qPCR Primer for PSEN1(NM_000021.3) Search again
Product ID:
HQP015123
(click here to view gene annotation page)
Powered by BiozSpecies:
Human
Symbol:
Alias:
ACNINV3, AD3, FAD, PS-1, PS1, PSNL1, S182
Gene Description:
presenilin 1
Target Gene Accession:
NM_000021.3(click here to view gene page)
Estimated Delivery:
Approximately 1-3 weeks, but may vary. Please email sales@genecopoeia.com or call 301-762-0888 to confirm ETA.
Important Note:
By default, qPCR primer pairs are designed to measure the expression level of the splice variant (accession number) you selected for this gene WITHOUT consideration of other possible variants of this gene. If this gene has multiple variants, and you would like to measure the expression levels of one particular variant, multiple variants, or all variants, please contact us for a custom service project at inquiry@genecopoeia.com.
Validated result:
|
|
| A | B |
|
Each All-in-One™ qPCR Primer is experimentally validated to yield a single dissociation curve peak and to generate a single amplification of the correct size for the targeted gene. A cDNA Pool, containing reverse transcript products of 8 different human tissue total RNA(Liver, Testis,Muscle,Thyroid,Brain,Spleen,Stomach,Small Intestine)),was used as the qPCR validation template. qPCR was performed using 0.2 µM primer with 2XAll-in-One™ qPCR Mix (Catalog#: QP001,QP002,QP004,QP005). Reactions were incubated for 10min. at 95°C, followed by 40 cycles of 95°C for 10 sec.; 60°C, 20 sec. and 72°C, 15sec. using Bio-Rad iQ5™ Instrument. At the end of the last cycle, temperature was increased from 72 to 95°C to produce a melting curve. Panel A: Validated Result for Amplification Curve; Panel B: Validated Result for Melting Curve. |
|
Summary
Alzheimer's disease (AD) patients with an inherited form of the disease carry mutations in the presenilin proteins (PSEN1; PSEN2) or in the amyloid precursor protein (APP). These disease-linked mutations result in increased production of the longer form of amyloid-beta (main component of amyloid deposits found in AD brains). Presenilins are postulated to regulate APP processing through their effects on gamma-secretase, an enzyme that cleaves APP. Also, it is thought that the presenilins are involved in the cleavage of the Notch receptor, such that they either directly regulate gamma-secretase activity or themselves are protease enzymes. Several alternatively spliced transcript variants encoding different isoforms have been identified for this gene, the full-length nature of only some have been determined. [provided by RefSeq].
Gene References into function
- Binding of the APP protease inhibitor pepstatin to presenilin 1 (PS1) is decreased in cells of a heterozygous carrier of the PS1 exon 9 deletion, suggesting that the PS1 mutation alters the inhibitor binding site.
- Here we present a novel cell-based reporter gene assay for the quantification of PS-controlled gamma-secretase cleavage of the Alzheimer amyloid precursor protein (APP).
- variable expression not a major determinant of risk for late-onset Alzheimer's disease
- enhancement of amyloid beta protein by Herp, and endoplasmic reticulum stress-inducible protein
- The PSEN1 mutation (P264L causes disease that begins with spastic paraparesis and is associated with dementia that is not of the Alzheimer type.
- inhibition of endoproteolysis by gamma-secretase inhibitors
- Notch receptor cleavage depends on but is not directly executed by presenilins
- Wild-type and mutated presenilins 2 trigger p53-dependent apoptosis and down-regulate presenilin 1 expression in HEK293 human cells and in murine neurons
- Neurotoxic mechanisms triggered by Alzheimer's disease-linked mutant M146L presenilin 1: involvement of NO synthase via a novel pertussis toxin target.
- Accelerated plaque accumulation, associative learning deficits, and up-regulation of alpha 7 nicotinic receptor protein in transgenic mice co-expressing mutant human presenilin 1 and amyloid precursor proteins
- It seems this novel missense substitution of serine for glycine, occurred at codon 266 in exon 8 of presenilin 1 is pathogenic, and findings provide a new clue to the etiology of the familial early onset dementia.
- The presence of a human presenilin 1 gene, normal or with an Alzheimer's disease mutation, leads to enhanced plasticity in the mouse brain.
- requirement for maturation and cell surface accumulation of nicastrin
- Alternative transcripts of presenilin 1 are associated with sporadic frontotemporal dementia, deletions having been identified within the exon 4-8 region.
- Expression of PS1 was found throughout myeloid development from CD34+ stem cells to platelets and neutrophils, and colocalized with amyloid precursor protein in cell-specific granules, suggesting a conserved function across different tissues.
- mutations of leucine 166 in presenilin-1 equally affect the generation of the Notch and APP intracellular domains independent of their effect on Abeta 42 production
- regulation by nicastrin and role in determining amyloid beta-peptide production via complex formation
- expression induced by interleukin-1beta and amyloid beta 42 peptide is potentiated by hypoxia in primary human neural cells
- interaction with GFAP epsilon
- Very early-onset familial Alzheimer's disease linked to G206V mutation in PS1
- mutations in PSEN1 increase Abeta42 production, inhibit cleavage of APP and notch
- presenilin 1 has a role in PI signal transduction, higher calcium, and apoptosis
- Presenilins are targeted as a biologically active complex with Nicastrin through the secretory pathway to the cell surface, suggesting a dual function of Presenilins in gamma-secretase processing and in trafficking.
- The genotype frequency of the Glu318Gly mutation in all Alzheimer's disease cases and controls in the Australian population was 2.8%.
- PS1/gamma-secretase contains PEN-2 and requires it for presenilin expression
- Presenilin-1 mutations alter K+ currents in the human neuroblastoma cell line, SH-SY5Y.
- In PS1 human-mutant knockin mice, PS1 is expressed in microglia & the M146V mutation confers a heightened sensitivity to LPS, as indicated by superinduction of inducible nitric oxide synthase & activation of MAP kinases.
- PS1 functions as a scaffold that rapidly couples beta-catenin phosphorylation through two sequential kinase activities independent of the Wnt-regulated Axin/CK1alpha complex.
- These data indicate that mammalian APH-1 (mAPH-1) along with presenilin 1 and nicastrin is probably a functional component of the gamma-secretase complex required for the intramembrane proteolysis of APP and Notch
- Presenilin1 mediates a dual intramembranous gamma-secretase cleavage of Notch-1.
- The PSEN1 gene -4,752 C/T polymorphism modifies the risk for AD.
- regulates intracellular trafficking and cell surface delivery of beta-amyloid precursor protein
- tetradecanoylphorbol acetate appears to activate the transcription of the PS1 gene by a mechanism which does not require the -10 Ets motif or the -6 CREB/AP1 motif
- Presenilin 1 regulates the glycosylation and intracellular trafficking of APP and select membrane proteins.
- Gamma-secretase activity is not involved in presenilin 1-mediated regulation of beta-catenin.
- regulation of proteolytic processing by PEN-2 and APH-1
- The missense mutation in exon 5 of presenilin-1 (PS-1) gene, found in this Alzheimer's disease family, may be one of the responsible PS-1 gene mutations for familial Alzheimer disease in Chinese.
- Our present findings suggest important implications for understanding CD44-dependent signal transduction and a potential role of PS/gamma-secretase activity in the functional regulation of adhesion molecules.
- APH-1 stabilizes the presenilin holoprotein in the complex, whereas PEN-2 is required for endoproteolytic processing of presenilin and conferring gamma-secretase activity to the complex.
- these studies provide evidence that the increased risk for AD associated with PSEN1 may result from genetic variations in the regulatory region, leading to altered expression levels of PSEN1 in neurons.
- A novel mutation (L250V) was found in the presenilin 1 gene in a Japanese case of familial Alzheimer's disease with myoclonus and generalized convulsion
- long-term potentiation in the CA1 was facilitated in the transgenic /presenilin 1/ rats with a different pattern of synaptic enhancement
- This clinical and pathological heterogeneity in patients with the same PSEN-1 mutation suggests phenotype modulation by genetic and/or epigenetic factors.
- GSK3beta activity increased in cells in the presence of mutant PS1 or in the absence of PS1 (PS1-/-). With increased GSK3beta activity, levels of kinesin light chain phosphorylation increased, and the amount of kinesin-I bound to organelles decreased
- PS1 is essential for gamma-secretase activity
- In vitro characterization of the presenilin-dependent gamma-secretase complex using a novel affinity ligand
- In a comparison of presenilin-1 protein in SH-SY5Y neuroblastoma cell lines over-expressing either the wild type or mutant PS1 proteins, there is a decrease in the expression levels of both proteins at the level of the cell membrane.
- Two novel presenilin-1 mutations (Y256S and Q222H) are associated with early-onset Alzheimer's disease.
- presenilins are multifunctional proteins with catalytic activity as well as roles in the generation, stabilization, and transport of the gamma-secretase complex
- These results suggest that PS1 associates intra-molecularly to form higher order complexes, which may be needed for endoproteolytic cleavage and/or gamma-secretase-associated activity.
- Presenilin 1 is downregulated by notch, which directly engages gamma-secretase
- PS1 has a role in N-Cad/CTF2 production and upregulating CREB-mediated transcription
- PS1 is not the core of the enzyme responsible for Notch1 cleavage but is clearly part of a partly known gamma-secretase complex implicated in the cleavage of different type 1 transmembrane proteins, e.g., Notch1 and amyloid precursor protein.
- Presenilin-1 is essential for efficient trafficking of N-cadherin from the endoplasmic reticulum to the plasma membrane.
- phosphorylation/dephosphorylation at the caspase recognition site provides a mechanism to reversibly regulate properties of PS1 in apoptosis.
- The authors describe a 28-year-old woman with histopathologically confirmed early onset Alzheimer disease characterized by severe frontal lobe involvement associated with a de novo mutation in the presenilin 1 gene (PSEN1)
- PS1 can regulate PLC activity and this function is gamma-secretase activity-dependent
- PS1 mutants do not simply alter the preferred cleavage site for gamma-secretase, but rather they have complex effects on the regulation of gamma-secretase and its access to substrates.
- Exon 9 deletion in presenilin 1 is associated with Alzheimer's disease
- capable of cleaving transmembrane proteins such as presenilin 1.
- PS1DeltaE9 molecules expressed in Spodoptera cells cells retain the ability to modulate amyloid beta protein levels.
- Clinical and cell culture phenotypes produced by these 2 codon 117 mutations are closely related suggesting that the pathogenic action of PS1 may involve effect on neurite outgrowth and endoproteolytic cleavage of the full-length protein.
- Presenilin 1 stabilizes the C-terminal fragment(C99) of the amyloid precursor protein independently of gamma-secretase activity.
- a sporadic early-onset patient with Alzheimer's disease, and this individual is a somatic mosaic for a mutation in the presenilin-1 gene, suggesting a novel molecular mechanism for AD
- Three missense mutations in presenilin 1(Ala246Glu in exon 7, Pro267Leu in exon 8, and Leu424Arg in exon 12) are found in Polish families with early-onset Alzheimer's disease.
- very low abundance, high mass (>/=670 kDa) heteromeric complexes of PS1 are associated with the highest gamma-secretase-specific activity
- gamma-secretase/presenilin has a role in processing and function of notch oncoproteins
- Data describe a synthetic peptide corresponding to the presenilin-1 exon 9 loop sequence, which was found to inhibit gamma-secretase in a cell-free enzymatic assay.
- A new 6-nucleotide insertional mutation at 715 in highly conserved exon 3 of the presenilin 1 gene causes an aggressive dementia that maintains the usual regional hierarchy of AD pathology while extending abnormalities into more widespread brain areas.
- PS1 activates P13K thus inhibiting GSK-3 activity and tau overphosphorylation: effects of Alzheimer disease mutations were studied.
- PS1 is involved in neuronal differentiation by a mechanism likely independent of endoproteolysis of the protein
- role of co-expression with nicastrin in rescuing loss of function mutant of APH-1
- monoubiquitination and endocytosis of Notch are a prerequisite for its presenilin-dependent cleavage
- This ssudy report a novel presenilin 1 (PSN1) mutation (Thr116Ile) in a woman with early onset Alzheimer's disease (AD).
- C terminus of PS1 is an activation peptide ligand for the PDZ domain of Omi/HtrA2 and may regulate the protease activity of Omi/HtrA2 after its release from the mitochondria during apoptosis.
- the -48C/T polymorphism in the PSN1 gene promoter is involved in the modulation of amyloid beta load in human AD, and is associated with DS.
- presenilin 1 (PS1)-derived fragments, mature nicastrin, APH-1, and PEN-2, associate with cholesterol-rich detergent insoluble membrane (DIM) domains of non-neuronal cells and neurons
- New V272A presenilin 1 mutation with very early onset subcortical dementia and parkinsonism.
- Mutations in exon 6 of presenilin-1 existed in the patients with familial Alzheimer's disease and sporadic Alzheimer's disease, and the two missense mutations were probably pathological by nature.
- Human presenilin 1 (PS1) is alternatively spliced, resulting in the presence or absence of a four-amino acid motif, VRSQ, in the PS1 N-terminus
- results suggest that the proximal two-thirds of the PEN-2 TMD1 is functionally important for endoproteolysis of PS1 holoproteins and the generation of PS1 fragments, essential components of the gamma-secretase complex
- Data show that the cytoplasmic tail of presenilin 1 (PS1) fulfills several functions required for complex formation, retention of unincorporated PS1 and gamma-secretase activity.
- presenilin/gamma-secretase exists as a mature complex at the cell surface and has roles in processing many adhesion molecules and receptors required for cell-cell interaction or intercellular signaling
- dimeric (NCSTN/APH-1) and trimeric (NCSTN/APH-1/PS1) intermediates of gamma-secretase complex assembly are retained within the ER and incorporation of the fourth binding partner (PEN-2) also occurs on immature NCSTN.
- M146L mutant PS-1 may predispose to both Pick's disease and AD by affecting multiple intracellular pathways involving tau phosphorylation and amyloid metabolism.
- knock down of anterior pharynx defective 1 homolog A (APH-1a), but not APH-1b, resulted in impaired maturation of nicastrin and reduced expression of presenilin 1, presenilin 2, and PEN-2 proteins
- The FAD (familial Alzheimer's disease)-linked PS1 variant produces transcriptome changes primarily by gain of aberrant function in transfected mice.
- aggressive Alzheimer-causing mutation in PS1 strongly reduced photolabeling by a transition-state analogue but not by helical peptides, providing biochemical evidence that the effect of this PS mutation is due to alteration of the active-site topography
- the mutant PSEN1 might play an important role in the pathogenetic process of both aggregation of alpha-synuclein into Lewy bodies and deposition of beta-amyloid into cotton wool plaques.
- GHR is subject to sequential proteolysis by metalloprotease and gamma-secretases, including PS1
- analysis of interaction between presenilin 1 and APP (amyloid beta precursor)
- PS1 mutations can lead to a wide spectrum of changes in the activity and specificity of gamma-secretase
- Of the nine pathogenic mutations found in 12 cases, three were in APP, one in PSEN2, and five in PSEN1, including two novel Greek mutations (L113Q and N135S)in Alzheimer disease
- Hydrophobic region 10 spans the membrane and the COOH terminal amino acids of PS1 lie in the extracytoplasmic space
- This novel presenilin 1 (PS1) gene mutation is likely to be causative of Chinese familial Alzheimer's disease.
- PS1 endoproteolysis occurs via intramolecular cleavage and does not require dimerization
- PS1/I213T KI mice had retarded acquisition of place learning in the water maze and in the visible platform subtest, were display whole-body startle to an auditory stimulus and a tighter grip on a horizontal grid.
- show that LRP colocalizes and interacts with endogenous PS1 and tested its role as a competitive substrate for gamma-secretase
- Altogether, our results demonstrated that phosphorylated CTFs can be the substrates of the gamma-secretase and that an increase in the phosphorylation of APP-CTFs facilitates their processing by gamma-secretase.
- The PS-1 mutations predominantly affect the CA regions with profound neurodegeneration, which contributes early and severe clinical features of familial Alzheimer's disease .
- Wild-type PS1 transgenes expressed in the mouse CNS support Abeta40 or Abeta42 production.
- results suggest that ubiquilin regulates presenilin fragment production
- Ncam1 is altered in transgenic mouse brains expressing FAD-linked PS1 variants, suggesting that expression of dominantly inherited mutant PS1 genes interferes with the normal Ncam1 expression via the p75 signaling pathway.
- Presenilin (PS)1 mutations interfere with PS2-mediated activity by reducing PS2 fragments
- PS1 has nine TM domains and the C terminus locates to the lumen/extracellular space
- Psen1 expression in neural progenitor cells is crucial for cortical development and reveal a novel role for neuroectodermal expression of Psen1 in development of the brain vasculature
- study is consistent with findings in sporadic Alzheimer disease of early problems with memory, visuospatial function, and particularly with executive function in PS1 mutation carriers
- cadherins mediate both the association of PS1 and beta-catenin and the effects of PS1 on the cellular levels of beta-catenin
- strong evidence provided that hydrophobic regions 8 and 9 are indeed membrane spanning and the integration of HR 8 into the membrane is dependent on the presence of HR 9
- endoproteolysis, N and C terminal fragment interactions, and the assembly and activity of gamma-secretase complexes are very conserved between PS1 and PS2
- mutational analyses revealed that the "NF" sequence within the TMD4 of PS1 is the minimal motif that is required for binding with PEN-2, promoting PS1 endoproteolysis and gamma-secretase activity
- Pen-2 may contribute to the activation of the gamma-secretase complex by directly binding to the TMD4 of PS1
- Clinical phenotypic heterogeneity of Alzheimer's disease associated with mutations of the presenilin-1 gene.
- Association with plakoglobin enhances the interaction of this molecule with Tcf-4 and prevents its binding to DNA.
- A novel PSEN1 mutation causes very-early-onset FAD with associated Lewy bodies. To our knowledge, this kindred has the earliest reported onset of pathologically confirmed FAD and dementia with Lewy bodies.
- These results suggest that PS1 regulates the growth and differentiation of endothelial progenitor cells through its beta-catenin-binding region.
- novel presenilin 1 L166H mutation in a pseudo-sporadic case of early-onset Alzheimer's disease.
- The authors describe four members of a family with a novel P284S presenilin 1 mutation presenting a clinical phenotype characterized by early-onset dementia, paratetraparesis, dysarthria, dysphagia, and marked involvement of brain white matter.
- Expression of familial-Azheimer-disease-linked mutant PS1DeltaE9 variants enhances the vulnerability of mouse neurons in the entorhinal cortex to perforant-pathway- lesion-induced cytotoxicity.
- the DAPT binding site as a novel functional domain within the PS C-terminal fragment that is distinct from the catalytic site or the substrate binding site
- protective role of the wild-type PS1 against the early onset familial Alzheimer disease mutation-induced amyloid pathology through a partial loss-of-function mechanism
- These results suggest that the precision of cleavage by the PS/gamma-secretase complex may be physiologically regulated by the subcellular location and conditions.
- Familial Alzheimer's disease (FAD)-linked Presenilin mutants lower the Ca(2+) content of intracellular stores.
- In conclusion, the Ala431Glu mutation in Presenilin 1 (PSEN1), is a prevalent cause of early-onset familial Alzheimer's disease in families from the State of Jalisco, Mexico.
- We demonstrate the existence of two physically different forms of gamma-secretase-associated PS1, one that is relatively proteinase K-sensitive and one that is significantly more PK-resistant.
- PS1 is an unprimed GSK-3beta substrate;important implications for regulation of PS1 function and the pathogenesis of Alzheimer's disease
- Data show that ubiquilin 1 interacts both with presenilin 1 (PS1) holoprotein and heterodimer and that the interaction between PS1 and ubiquilin 1 takes place near the cell surface.
- Data indicate that presenilin-1 has a nine-transmembrane domain topology with the COOH terminus exposed to the lumen/extracellular surface.
- the Ala431Glu substitution in the PSEN1 gene is not an uncommon cause of early-onset autosomal dominant Alzheimer disease in persons of Mexican origin
- PS1 mutations associated with FAD abolish production of the N-cadherin intracellular fragment
- Our data reveal that the Presenilin-1 V97L variant can elevate Abeta42 levels both intracellularly and extracellularly, and was a potentially pathogenic mutation for this Chinese FAD pedigree.
- PSEN1 gene mutations resulting in large increases in secreted Abeta42 levels or loss of PSEN1 exons 8 or 9 may cause Alzheimer disease with spastic paraparesis and cotton wool plaques.
- In a case-control association study in an Italian population there is a significant association in PSEN-1 carriers of a glutamic acid318glycine mutation and familial Alzheimer's disease.
- expression of mutant PS1 in cultured neurons depresses synaptic transmission by causing a physical reduction in the number of synapses
- PS1 may be involved in neuritogenesis and morphological change in SH-SY5Y cells, and P117L mutation may linked to Alzheimer's disease by different mechanisms
- 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.
- Presenilin mutations linked to familial Alzheimer's disease cause an imbalance in phosphatidylinositol 4,5-bisphosphate metabolism.
- The elevated Abeta42/Abeta40 ratio observed with mutant PS1-expressing cells may be due to reduced Abeta40 production not increased Abeta42 production.
- provides comprehensive profile of non-cognitive behaviors of APP/PS1 transgenic mouse model; reveals behavior impairments that may be pertinent to behavior seen in AD patients
- PS/gamma-secretase-mediated cleavage of LAR controls LAR-beta-catenin interaction, suggesting an essential role for PS/gamma-secretase in the regulation of LAR signaling
- reduced presenilin proteolytic function leads to increased Abeta42/Abeta40 in Alzheimer disease (Review)
- mutations in Alzheimer disease (Review)
- RNA interference of PS1 or Notch1 can block Notch signaling and consequently induce growth inhibition of HeLa cells.
- In this work, spectroscopic data is presented that does not correlate structure or stability of the proposed PS-I autoinhibitory module with pathogenicity.
- PC12 cells were stably transfected with familial mutations and were examined for gamma-secretase-dependent proteolysis of p75NTR. The presence of the M146V mutation was shown to significantly increase cleavage of p75NTR.
- results also suggest that PSEN1 mutations can cause Alzheimer's disease with a large range in age of onset, spanning both early- and late-onset Alzheimer's disease
- abnormal activation of glycogen synthase kinase 3beta can reduce neuronal viability and synaptic plasticity via modulating Presenilin 1/N-cadherin/beta-catenin interaction and thus have important implications in the pathophysiology of Alzheimer disease.
- Exogenous cholesterol and compartmentalization in neuroblastoma cells play a relevant role in regulating the transcription of presenilin 1.
- APP and PS1 are closely associated in the centrosomes of the H4 cell
- No association with late-onset form of Alzheimer's disease.
- Many familial Alzheimer disease mutations in presenilins are loss-of-function mutations affecting endoplasmic reticulum calcium (Ca2+) leak activity, consistent with the potential role of disturbed Ca2+ homeostasis in Alzheimer disease pathogenesis.
- activation of PS1 transcription by ERM was eliminated with increasing levels of CHD3
- Association of a presenilin 1 S170F mutation with a novel Alzheimer disease molecular phenotype.
- The novel PSEN1 mutation identified in this patient adds to the diverse list of existing mutations causing early onset Alzheimer disease associated with spastic paraparesis.
- Intense and focal positron emission tomography agent (Pittsburgh compound-B) retention is observed in the striatum of all presenilin-1 mutation carriers studied (aged 35-49 years and at high risk for Alzheimer disease).
- all known gamma-secretase complexes are active in APP processing and that all combinations of APH-1 variants with either familial Alzheimer mutant PS1 or PS2 support pathogenic Abeta(42) production
- aggressive presenilin-1 mutations cause insensitivity to Abeta42-lowering nonsteroidal anti-inflammatory drugs and gamma-secretase inhibitors
- summarizes work focused on identifying and studying domains in PS1 that are critical for mediating gamma-secretase activity
- A new mutation (496_498delCTT at codon 166) in the 3d transmembrane domain of exon 6 was associated with the 'typical' presentation of early-onset AD seen in most exon 6 mutations, but not in deletions at other sites.
- These data indicate that the presence of an FAD-associated mutant human PS1 transgene is associated with redistribution of the APP and APP CTFs in brain neurons toward TGN-enriched fractions.
- We sequenced nine spastic paraparesis genes in three Alzheimer's disease families with PSEN1 exon 9 deletions. We did not observe any correlation of polymorphisms or mutations in the nine spastic paraparesis genes.
- a single point mutation, p.L420R, is the mutation responsible for early onset Alzheimer disease, seizures and cotton wool plaques without spastic paraparesis in a family
- We describe a case of a young patient suffering from a rapidly progressive cognitive decline, associated with delusions, myoclonus and seizures and with no family history for dementia anddemonstrated a de novo presenilin 1 mutation.
- Presenilin-1 2/2 genotype is a risk factor for late onset Alzheimer disease in the Spanish population, and probably, for Europeans.
- Healthy carriers of the E280A presenilin-1 gene mutation scored significantly lower than noncarriers on naming of famous faces. Cognitive changes in lexical-semantic tasks can be detected before the clinical diagnosis of probable familial Alzheimer's.
- the familial Alzheimer's disease-linked PS1 mutation accelerates the cleavage of caspase-4 under the endoplasmic reticulum stress
- The amount of Abeta(42) produced by cells expressing 10 different familial Alzheimer disease is associated with mutations in presenilin 1.
- present study demonstrates that PSEN1 linked autosomal dominant early onset Alzheimer's disease has to be considered, even when ataxia precedes dementia, the Pro117Ala mutation being responsible for a predominant precocious ataxia
- L286P is a novel mutation in PSEN1 that causes familial early-onset AD and brain haematomas related to amyloid angiopathy.
- neurogenesis is decreased with degrees of Abeta pathology, and that there is no gender difference in their proliferation in APPswe/PS1dE9 transgenic mice
- Overexpression of presenilin-1 increased HIF-1beta, suggesting that HIF is downstream of presenilin
- In the PS1 familial Alzheimer's disease brain, cyclin D1 accumulation may occur and lead to neuronal apoptosis secondary to an abortive entry into the cell cycle.
- Mature integrin beta1 with increased expression level is delivered to the cell surface, which results in an increased cell surface expression level of mature integrin beta 1 in presenilin (PS)1 and PS2 double-deficient fibroblasts.
- PS1 can interact with AChE and influence its expression, supporting the notion of cholinergic-amyloid interrelationships.
- Data show that a presenilin-1 280Glu-->Ala mutation alters C-terminal amyloid precursor protein processing, yielding longer amyloid beta peptides, and discuss the implications for Alzheimer's disease.
- Data show that the E280A mutation in presenilin 1 is not associated with increased production of amyloid-beta in non-neuronal peripheral tissues, which is in contrast to the expectation in a gamma-secretase gain of function.
- We report a late onset familial Alzheimer's disease: novel presenilin 2 mutation and PS1 E318G polymorphism.
- The tendency for a higher prevalence of headaches held for different PSEN1 and APP mutations but was not significant unless all families were combined.
- I213T mutant presenilin-1/gamma-secretase in cell models and knock-in mouse brains: familial Alzheimer disease-linked mutation impairs gamma-site cleavage of amyloid precursor protein C-terminal fragment beta
- PSEN1 and APP gene mutations may not be uncommon in Korean patients with early-onset Alzheimer's disease
- pathological levels of Abeta42 may be caused by the negative effects of a novel presenilin-1 mutant (V97L) on insulin-degrading enzyme expression and activity
- The P117A variant is a novel mutation in PSEN1, which causes early-onset AD in an autosomal dominant manner.
- did not find any modification of the A beta(1-42)/A beta(1-40) ratio, suggesting that this double mutation might be involved in early-onset AD etiopathogenesis by affecting a PSEN-1 function other than gamma-secretase activity.
- Enhanced Ca2+ release from the endoplasmic reticulum as a result of the specific interaction of mutant presenilin 1-Met146Leu with the inositol 1,4,5-trisphosphate receptor stimulates amyloid beta processing, an important feature of Alzheimer's pathology
- first description of neuropathologic findings in early onset familial Alzheimer disease(EOFAD)due to N135S PSEN1 mutation; clinical phenotype was remarkable for spastic dysarthria, limb spasticity & seizures, in addition to more typical features of EOFAD
- although PSEN1 mutations are the most frequent cause, the MAPT R406W mutation is an important cause of early-onset familial dementia clinically diagnosed as Alzheimer's disase in Japanese
- SERCA activity is diminished in fibroblasts lacking both PS1 and PS2 genes, despite elevated SERCA2b steady-state levels.
- A novel mutation in exon 8 of the PSEN1 gene (V261L) was associated with early-onset autosomal dominant Alzheimer's disease & spastic paraparesis in 3 family members.
- necrosis factor-alpha-elicited stimulation of gamma-secretase is mediated by c-Jun N-terminal kinase-dependent phosphorylation of presenilin and nicastrin
- Enhanced sensitivity to trophic withdrawal in the cells transfected with the two Chinese PS1 mutations may contribute to the neuron apoptosis.
- The age-related elevation of oxidative damage was observed in human mutant PS-1 mice brain compared to that of wild-type mice brain.
- analysis of model of the gamma-secretase complex subunit architecture and demonstration of the close proximity of the C-terminal fragment of presenilin with APH-1
- the present results reinforce the possible involvement of PSEN1 in sporadic Alzheimer's disease
- results support a model whereby the PS gamma-secretase activity is essential in maintaining neuronal viability, and the PS1 loop domain modulates neuronal homeostasis through cell cycle and cytoplasmic p53 control
- TRAF6 and interleukin receptor-associated kinase 2 are novel binding partners for PS1, and IL-1R1 is a new substrate for presenilin-dependent gamma-secretase cleavage
- Data show that familial Alzheimer's disease cases with mutations in the presenilin 1 gene exhibit significantly more tau-positive neurofibrillary tangle than sporadic Alzheimer's disease cases.
- the 1/1 presenilin-1 genotype does not increase the risk of developing late-onset Alzheimer's disease in the Turkish population