ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2006
Presenilin-dependent gamma-secretase-mediated control of p53-associated cell death in Alzheimer's disease.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.
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Who cites it
72 citing papers in PubMed, 160 citations in OpenAlex.
- p53: from understanding its structure to advances in therapeutic targeting.Signal transduction and targeted therapy · 2026Review
- Decoding the mechanisms of amyloid-β in synaptic toxicity.Journal of Alzheimer's disease : JAD · 2026Review
- Presenilins as hub proteins controlling the endocytic and autophagic pathways and small extracellular vesicle secretion.Journal of extracellular vesicles · 2025Article
- The AICD interactome: implications in neurodevelopment and neurodegeneration.Biochemical Society transactions · 2024Review
- MicroRNAs: pioneering regulators in Alzheimer's disease pathogenesis, diagnosis, and therapy.Translational psychiatry · 2024Review
- Secretase promotes AD progression: simultaneously cleave Notch and APP.Frontiers in aging neuroscience · 2024Review
- Amyloid β-based therapy for Alzheimer's disease: challenges, successes and future.Signal transduction and targeted therapy · 2023Review
- Tumor suppressor p53 regulates heat shock factor 1 protein degradation in Huntington's disease.Cell reports · 2023Article
- Review
- Physiological Roles of Monomeric Amyloid-β and Implications for Alzheimer's Disease Therapeutics.Experimental neurobiology · 2022Review
- Parkin as a Molecular Bridge Linking Alzheimer's and Parkinson's Diseases?Biomolecules · 2022Review
- Oncogenic Pathways in Neurodegenerative Diseases.International journal of molecular sciences · 2022Review
- Regulation of gene expression by the APP family in the adult cerebral cortex.Scientific reports · 2022Article
- Extracellular vesicle miRNAs in breast milk of obese mothers.Frontiers in nutrition · 2022Article
- Mitochondrial Targeting of Amyloid-β Protein Precursor Intracellular Domain Induces Hippocampal Cell Death via a Mechanism Distinct from Amyloid-β.Journal of Alzheimer's disease : JAD · 2022Article
- Rare CASP6N73T variant associated with hippocampal volume exhibits decreased proteolytic activity, synaptic transmission defect, and neurodegeneration.Scientific reports · 2021Article
- Melatonin Induction of APP Intracellular Domain 50 SUMOylation Alleviates AD through Enhanced Transcriptional Activation and Aβ Degradation.Molecular therapy : the journal of the American Society of Gene Therapy · 2021Article
- Therapeutic potential of parkin as a tumor suppressor via transcriptional control of cyclins in glioblastoma cell and animal models.Theranostics · 2021Article
- Quinovic Acid Impedes Cholesterol Dyshomeostasis, Oxidative Stress, and Neurodegeneration in an Amyloid-Oxidative medicine and cellular longevity · 2020Article
- The Regulation of microRNAs in Alzheimer's Disease.Frontiers in neurology · 2020Review
12 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Presenilins (PSs) are part of the gamma-secretase complex that produces the amyloid beta-peptide (Abeta) from its precursor [beta-amyloid precursor protein (betaAPP)]. Mutations in PS that cause familial Alzheimer's disease (FAD) increase Abeta production and trigger p53-dependent cell death. We demonstrate that PS deficiency, catalytically inactive PS mutants, gamma-secretase inhibitors, and betaAPP or amyloid precursor protein-like protein 2 (APLP2) depletion all reduce the expression and activity of p53 and lower the transactivation of its promoter and mRNA expression. p53 expression also is diminished in the brains of PS- or betaAPP-deficient mice. The gamma- and epsilon-secretase-derived amyloid intracellular C-terminal domain (AICD) fragments (AICDC59 and AICDC50, respectively) of betaAPP trigger p53-dependent cell death and increase p53 activity and mRNA. Finally, PS1 mutations enhance p53 activity in human embryonic kidney 293 cells and p53 expression in FAD-affected brains. Thus our study shows that AICDs control p53 at a transcriptional level, in vitro and in vivo, and that FAD mutations increase p53 expression and activity in cells and human brains.
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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.