ArticleProceedings of the National Academy of Sciences of the United States of America2002
Wild-type and mutated presenilins 2 trigger p53-dependent apoptosis and down-regulate presenilin 1 expression in HEK293 human cells and in murine neurons.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 39 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
39 citing papers in PubMed, 1 synthesis or guideline pooled it, 132 citations in OpenAlex.
- Mutations in presenilin 2 and its implications in Alzheimer's disease and other dementia-associated disorders.Clinical interventions in aging · 2015Pooled it
- Review
- PSEN2 and ABCA7 variants causing early-onset preclinical pathological changes in Alzheimer's disease: a case report and literature review.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2023Review
- Notch signaling pathway: a comprehensive prognostic and gene expression profile analysis in breast cancer.BMC cancer · 2022Article
- Potential of Therapeutic Small Molecules in Apoptosis Regulation in the Treatment of Neurodegenerative Diseases: An Updated Review.Molecules (Basel, Switzerland) · 2022Review
- Parkin as a Molecular Bridge Linking Alzheimer's and Parkinson's Diseases?Biomolecules · 2022Review
- Therapeutic potential of parkin as a tumor suppressor via transcriptional control of cyclins in glioblastoma cell and animal models.Theranostics · 2021Article
- Specificity of presenilin-1- and presenilin-2-dependent γ-secretases towards substrate processing.Journal of cellular and molecular medicine · 2018Article
- Inhibition of the Neuronal Calcium Sensor DREAM Modulates Presenilin-2 Endoproteolysis.Frontiers in molecular neuroscience · 2018Article
- Overexpression of N141I PS2 increases γ-secretase activity through up-regulation of Presenilin and Pen-2 in brain mitochondria of NSE/hPS2m transgenic mice.Laboratory animal research · 2016Article
- Presenilin 2 overexpression is associated with apoptosis in Neuro2a cells.Translational neuroscience · 2016Article
- Interleukin-1β causes excitotoxic neurodegeneration and multiple sclerosis disease progression by activating the apoptotic protein p53.Molecular neurodegeneration · 2014Article
- BACE1 is at the crossroad of a toxic vicious cycle involving cellular stress and β-amyloid production in Alzheimer's disease.Molecular neurodegeneration · 2012Review
- RNAi-mediated inhibition of presenilin 2 inhibits glioma cell growth and invasion and is involved in the regulation of Nrg1/ErbB signaling.Neuro-oncology · 2012Article
- Nuclear factor-κB regulates βAPP and β- and γ-secretases differently at physiological and supraphysiological Aβ concentrations.The Journal of biological chemistry · 2012Article
- α-Secretase-derived fragment of cellular prion, N1, protects against monomeric and oligomeric amyloid β (Aβ)-associated cell death.The Journal of biological chemistry · 2012Article
- Tip60 HAT activity mediates APP induced lethality and apoptotic cell death in the CNS of a Drosophila Alzheimer's disease model.PloS one · 2012Article
- Exercise and early-onset Alzheimer's disease: theoretical considerations.Dementia and geriatric cognitive disorders extra · 2012Article
- γ-Secretase complexes containing caspase-cleaved presenilin-1 increase intracellular Aβ(42) /Aβ(40) ratio.Journal of cellular and molecular medicine · 2011Article
- BACE and gamma-secretase characterization and their sorting as therapeutic targets to reduce amyloidogenesis.Neurochemical research · 2010Review
Corrections and comments
- Erratum issuedMattson Marc P [corrected to Mattson Mark P]
Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Presenilins 1 and 2 are two homologous proteins that, when mutated, account for most early onset Alzheimer's disease. Several lines of evidence suggest that, among various functions, presenilins could modulate cell apoptotic responses. Here we establish that the overexpression of presenilin 2 (PS2) and its mutated form Asn-141-Ile-PS2 alters the viability of human embryonic kidney (HEK)293 cells as established by combined trypan blue exclusion, sodium 3'-[1-(phenylamino-carbonyl)-3,4-tetrazolium]-bis(4-methoxy-6-nitro)benzene sulfonic acid hydrate assay, and propidium iodide incorporation FACS analyses. The two parent proteins increase the acetyl-DEVD-al-sensitive caspase-3-like activity in both HEK293 cells and Telencephalon specific murine neurons, modulate Bax and bcl-2 expressions, and enhance cytochrome C translocation into the cytosol. We show that overexpression of both wild-type and mutated PS2 increases p53-like immunoreactivity and transcriptional activity. We also establish that wild-type- and mutated PS2-induced caspase activation is reduced by p53 antisense approach and by pifithrin-alpha, a chemical inhibitor of p53. Furthermore, mouse fibroblasts in which the PS2 gene has been knocked out exhibited strongly reduced p53-transcriptional activity. Finally, we establish that the overexpression of both wild-type and mutated PS2 is accompanied by a drastic reduction of endogenous presenilin 1 (PS1) expression. Interestingly, pifithrin-alpha diminished endogenous PS2 immunoreactivity, whereas the inhibitor increases PS1 expression. Altogether, our data demonstrate that wild-type and familial Alzheimer's disease-linked PS2 trigger apoptosis and down-regulate PS1 expression through p53-dependent mechanisms.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.