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Presenilin-1 targeted morpholino induces cognitive deficits, increased brain Abeta1-42 and decreased synaptic marker PSD-95 (show DLG4 Proteins)
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.
Data indicate a novel role for PS1 in regulating TREM2 (show TREM2 Proteins) intracellular trafficking and pathophysiological function.
A subset of early-onset Alzheimer's disease is inherited as an autosomal-dominant trait and is associated with mutations in the genes encoding presenilin 1.
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 (show PCSK7 Proteins) 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 (show APP Proteins) 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 (show APP Proteins) 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 (show APP Proteins) level, AD-related tau cytoskeletal pathology, and SH-SY5Y cell apoptosis.
Under conditions of reduced glucose, the PS1/gamma-secretase system decreases neuronal losses by suppressing miR (show MLXIP Proteins)-212 and increasing its target survival factor, PEA15 (show PEA15 Proteins). These observations have implications for mechanisms of neuronal death under conditions of reduced glucose and may provide targets for intervention in neurodegenerative disorders.
PS1 phosphorylated at Ser367 has an antiamyloidogenic function, promoting autophagosome-lysosome fusion and increasing betaCTF degradation
Fibroblast growth factor (FGF1 (show FGF1 Proteins) and FGF2 (show FGF2 Proteins)), but not vascular endothelial growth factor (VEGF (show VEGF Proteins)) rescued Psen1-/- cells from serum starvation induced apoptosis.In the absence of serum, FGF2 (show FGF2 Proteins) immunoreactivity was distributed diffusely in cytoplasmic and nuclear vesicles of wt and Psen1-/- cells, as levels of FGF2 (show FGF2 Proteins) in nuclear and cytosolic fractions were not significantly different.
Upregulated p53 (show TP53 Proteins)-p21 Signaling is linked with presenilin 1 mutants
The cognitive function of APP (show APP Proteins)/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 (show PSENEN Proteins) and PS1 are sufficient to form a functionally active gamma-secretase that is capable of catalyzing the processing of Notch (show NOTCH1 Proteins). This finding strongly suggests that Pen-2 (show PSENEN Proteins) 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 (show SYT1 Proteins) level and presenilin 1-synaptotagmin 1 (show SYT1 Proteins) 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 (show CA2 Proteins)+) signals in PS1dE9 mutant mice.
Loss of PS1 is associated with cognitive impairment.
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