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Presenilin-1 targeted morpholino induces cognitive deficits, increased brain Abeta1-42 and decreased synaptic marker PSD-95 (zeige DLG4 Proteine)
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 (zeige PSEN2 Proteine) plays a more prominent role in Notch (zeige NOTCH1 Proteine) signalling and embryo development in zebrafish than in mammals, and that the effect of reduced Psen2 (zeige PSEN2 Proteine) can be ameliorated by Psen1 loss.
We describe here the generation of functional astrocytes from induced pluripotent stem cells (iPSCs) derived from AD patients with PSEN1 DeltaE9 mutation, as well as healthy and gene-corrected isogenic controls.
The data of this study suggest a deficiency of PE and LPC (zeige PCSK7 Proteine) levels in the temporal cortex from Alzheimer's Disease-PSEN1(E280A) and Sporadic Alzheimer's Disease brains with respect to healthy brains.
3 distinct conformations of gamma-secretase (open, semiopen, and closed) differ by tilting of helices 2 and 3 of PS1, directly controlling active site availability. The semiopen conformation shows the best fit of Abeta (zeige APP Proteine) peptides, i.e., longer residence before release and by inference more trimming. The closed, hydrophobic conformation is largely inactive and the open conformation is active but provides less optimal inte...
phosphorylation of PS1 at Ser367 does not affect gamma-secretase activity, but has a dramatic effect on Abeta (zeige APP Proteine) levels in vivo
This study demonstrated that the Precuneus cortex brain wave in PSEN1 E280A Family at Risk of Developing Alzheimer's disease.
PSEN1 gene polymorphisms in Caucasian Alzheimer's disease
A case control study confirms PSEN1 rs17125721 as a risk factor for familial AD in Brazil.
PS1 increases the level of U1snRNA accompanied with the adverse change of Abeta (zeige APP Proteine) level, AD-related tau cytoskeletal pathology, and SH-SY5Y cell apoptosis.
Study reports a novel PSEN1 K311R mutation in two Chinese families with late-onset Alzheimer's disease. The mutation was located within the hydrophilic loop domain of PSEN1 C-terminal cytoplasmic loop and enhanced Abeta42 production and tau phosphorylation in HEK293-APP695wt cells.
Induced pluripotent stem cells derived from somatic cells of familial Alzheimer disease patients carrying PSEN1 mutations exhibit premature neuronal differentiation with decreased proliferation and increased apoptosis.
PS1 phosphorylated at Ser367 has an antiamyloidogenic function, promoting autophagosome-lysosome fusion and increasing betaCTF degradation
Fibroblast growth factor (FGF1 (zeige FGF1 Proteine) and FGF2 (zeige FGF2 Proteine)), but not vascular endothelial growth factor (VEGF (zeige VEGF Proteine)) rescued Psen1-/- cells from serum starvation induced apoptosis.In the absence of serum, FGF2 (zeige FGF2 Proteine) immunoreactivity was distributed diffusely in cytoplasmic and nuclear vesicles of wt and Psen1-/- cells, as levels of FGF2 (zeige FGF2 Proteine) in nuclear and cytosolic fractions were not significantly different.
Upregulated p53 (zeige TP53 Proteine)-p21 Signaling is linked with presenilin 1 mutants
The cognitive function of APP (zeige APP Proteine)/PS1 mice was impaired at 10months of age; moreover, the hypermetabolic state identified in various brain regions at 5months of age was also significantly decreased.
Using knockout cell lines in combination with siRNA and immunoprecipitation approaches, our data clearly demonstrated that the Pen-2 (zeige PSENEN Proteine) and PS1 are sufficient to form a functionally active gamma-secretase that is capable of catalyzing the processing of Notch (zeige NOTCH1 Proteine). This finding strongly suggests that Pen-2 (zeige PSENEN Proteine) is the most crucial component in gamma-secretase complex in addition to presenilin that functions as the catalytic subunit.
that reduction in the synaptotagmin 1 (zeige SYT1 Proteine) level and presenilin 1-synaptotagmin 1 (zeige SYT1 Proteine) interactions in AD brain may present molecular underpinning of the pathogenic presenilin 1 conformation
PS1 plays a crucial role in the cerebrovascular system and the vascular reactivity is decreased through altered Ca(2 (zeige CA2 Proteine)+) signals in PS1dE9 mutant mice.
Loss of PS1 is associated with cognitive impairment.
Cultured hippocampal neurons expressing mutant PS1 had attenuated CCE that was associated with destabilized dendritic spines, which were rescued by either gamma-secretase inhibition or overexpression of STIM1 (zeige STIM1 Proteine).
Conditionally targeted deletion of PSEN1 leads to diastolic heart dysfunction and ultrastructural cardiomyocyte abnormalities.
maternal dietary betaine supplementation during gestation inhibits hepatic cell proliferation in neonatal piglets, at least partly, through epigenetic regulation of hepatic CCND2 (zeige CCND2 Proteine) and PSEN1 genes via a STAT3 (zeige STAT3 Proteine)-dependent pathway
gamma-Secretase and presenilin mediate cleavage and phosphorylation of vascular endothelial growth factor receptor-1 (zeige FLT1 Proteine)
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