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Using an antisense morpholino oligonucleotide, study blocked induction of PS1IV isoform that normally occurs under hypoxia,identified gene regulatory networks that are modulated by PS1IV: observed changes in expression of genes controlling inflammation, vascular development, the UPR, protein synthesis, calcium homeostasis, catecholamine biosynthesis, TOR signaling, and cell proliferation
We identified psen1 as a regulator of the development of histaminergic neurons in zebrafish
These results suggest that Psen2 (show PSEN2 Proteins) plays a more prominent role in Notch (show NOTCH1 Proteins) signalling and embryo development in zebrafish than in mammals, and that the effect of reduced Psen2 (show PSEN2 Proteins) can be ameliorated by Psen1 loss.
PSEN1 rare variants collectively show a significant association with the brain atrophy in regions preferentially affected by late-onset Alzheimer's disease
Tspan3 (show TSPAN3 Proteins) is a central endocytic membrane component regulating the expression of ADAM10 (show ADAM10 Proteins), presenilin and the amyloid precursor protein (show APP Proteins).
Familial Alzheimer's disease-associated PS1 mutations induce disease pathogenesis by increasing Abeta42/Abeta40 ratio.
a novel mutation PSEN1 c.1156T>A, p.F386I was detected in a Chinese family with FAD (show BRCA2 Proteins). The mutation cosegregates with affected family members suggesting a mutagenic and probably pathogenic effect.
proapoptotic signaling pathways c-Jun NH2-terminal kinase (show MAPK8 Proteins) and p38 mitogen-activated protein kinase (show MAPK14 Proteins) maintained PSEN1-mediated negative regulation in K239N but not in E120G-bearing cells
increased mitochondrial calcium due to the gain-of-function enhancement of IP3R (show ITPR1 Proteins) channels in the cells expressing PS1-M146L leads to the opening of permeability transition pore in high conductance state.
The search for the genetic factors contributing to Alzheimer disease (AD) has evolved tremendously throughout the years. It started from the discovery of fully penetrant mutations in Amyloid precursor protein (show APP Proteins), Presenilin 1, and Presenilin 2 (show PSEN2 Proteins) as a cause of autosomal dominant AD
The authors now show that the very little Abeta (show APP Proteins) generated by PS1 L435F mutant consists primarily of Abeta43, a highly amyloidogenic species which was overlooked in previous studies of this mutant.
APP (show APP Proteins) + PS1 double transgenic rats had altered serum Abeta42 and Abeta42/Abeta40 levels, brain histopathology and cognitive behavior. APP (show APP Proteins) rat brain had many histopathogical abnormalities that are often seen in Alzheimer's disease brains, but their memory did not show significant impairment during the behavioral testing. APP (show APP Proteins) + PS1 rats showed brain pathology as well as reduced memory retention compared to the APP (show APP Proteins) and the ...
gamma-Secretase is a multimeric membrane protease involved in processing of the amyloid precursor protein (show APP Proteins) with high clinical relevance as mutations in its catalytic subunit (Presenilin) cause early-onset Alzheimer's disease
Study shows that the binding of HSF-1 (show HSF1 Proteins), Cdx1 (show CDX1 Proteins), Ets-1 (show ETS1 Proteins) and Sp1 (show SP1 Proteins) to Presenilin 1 promoter and that of Nkx2.2 (show Nkx2-2 Proteins), HFH-2 (show FOXD3 Proteins), Cdx1 (show CDX1 Proteins) and NF-kappaB (show NFKB1 Proteins) to Presenilin 2 (show PSEN2 Proteins) promoter regulate their differential expression during brain development.
conclusion that the PSEN1 mutations are extreme examples of the previously proposed ''dysfunction'' of gamma-secretase that characterizes familial Alzheimer's disease
PS1 expression is triggered by glutamate (show GRIN1 Proteins) through p38alpha (show MAPK14 Proteins), contributing to the excitotoxic stimulus of EW
amino acid sensing of mechanistic target of rapamycin (show FRAP1 Proteins) complex 1 (mTORC1) is dysregulated in cells deficient in presenilin.
the G206D mutation reduced presenilin-1-presenilin enhancer 2 (show PSENEN Proteins) interaction, but did not abolish gamma-secretase formation and presenilin-1 endoproteolysis
This study deals with the effect of attenuated endoproteolysis of PS1 on store-operated calcium (SOC (show UBXN11 Proteins)) entry in neuronal cells and mouse fibroblasts with double knockouts of PS1 and PS2 (show PDCD6 Proteins)
Results showed that epigenetic mechanisms play a pivotal role in transcriptional regulation of PS1 and PS2 (show PDCD6 Proteins) during cerebral cortical development
lactate levels remained elevated with age and increased aerobic glycolysis enzyme expression correlated with poorer memory performance in APP (show APP Proteins)/PS1 mice
PS1 deficiency depletes vATPase (show ATP6V1H Proteins), impairing lysosomal acidification and calcium homeostasis.
maternal dietary betaine supplementation during gestation inhibits hepatic cell proliferation in neonatal piglets, at least partly, through epigenetic regulation of hepatic CCND2 (show CCND2 Proteins) and PSEN1 genes via a STAT3 (show STAT3 Proteins)-dependent pathway
gamma-Secretase and presenilin mediate cleavage and phosphorylation of vascular endothelial growth factor receptor-1 (show FLT1 Proteins)
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.
, presenilin 1 (Alzheimer disease 3)
, presenilin-1 isoform I-463
, presenilin-1 isoform I-467
, presenilin 1
, presenilin alpha