ArticleProceedings of the National Academy of Sciences of the United States of America2000
Presenilin-1 regulates the neuronal threshold to excitotoxicity both physiologically and pathologically.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 45 citations in OpenAlex.
- Article
- Blood-Based Biomarkers for Post-Stroke Cognitive Impairment.Current issues in molecular biology · 2026Review
- Modular Phosphoprotein Signatures Link Rac1 Inhibition to Neurite Morphogenesis in a Dose-Dependent Manner.Developmental neuroscience · 2026Article
- A unique subpopulation of wild-type neurons recapitulating familial Alzheimer's disease phenotypes.Cell death & disease · 2025Article
- Curbing Rhes Actions: Mechanism-based Molecular Target for Huntington's Disease and Tauopathies.CNS & neurological disorders drug targets · 2024Review
- Mouse models of Alzheimer's disease cause rarefaction of pial collaterals and increased severity of ischemic stroke.Angiogenesis · 2019Article
- Familial Alzheimer's Disease Lymphocytes Respond Differently Than Sporadic Cells to Oxidative Stress: Upregulated p53-p21 Signaling Linked with Presenilin 1 Mutants.Molecular neurobiology · 2017Article
- Nucleic Acid-Based Theranostics for Tackling Alzheimer's Disease.Theranostics · 2017Review
- Presenilin 1 promotes trypsin-induced neuroprotection via the PAR2/ERK signaling pathway. Effects of presenilin 1 FAD mutations.Neurobiology of aging · 2016Article
- Chronic Glutamate Toxicity in Neurodegenerative Diseases-What is the Evidence?Frontiers in neuroscience · 2015Review
- Endogenous expression of FAD-linked PS1 impairs proliferation, neuronal differentiation and survival of adult hippocampal progenitors.Molecular neurodegeneration · 2013Article
- Presenilin transgenic mice as models of Alzheimer's disease.Brain structure & function · 2010Review
- The presenilin-1 familial Alzheimer's disease mutation P117L decreases neuronal differentiation of embryonic murine neural progenitor cells.Brain research bulletin · 2009Article
- Dysregulated IP3 signaling in cortical neurons of knock-in mice expressing an Alzheimer's-linked mutation in presenilin1 results in exaggerated Ca2+ signals and altered membrane excitability.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2004Article
- Increased fibrillar beta-amyloid in response to human clq injections into hippocampus and cortex of APP+PS1 transgenic mice.Neurochemical research · 2003Article
- Transgenic mouse models of Alzheimer's disease.The Mount Sinai journal of medicine, New YorkReview
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Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
A direct pathophysiological role of Familial Alzheimer's Disease (FAD)-associated Presenilin 1 (PS1) mutations in neuronal vulnerability remains a controversial matter. We evaluated the relationship between PS1 and excitotoxicity in four different experimental models of neurotoxicity by using primary neurons from (i) transgenic (tg) mice overexpressing a human FAD-linked PS1 variant (L286V mutation), (ii) tg mice overexpressing human wild-type (wt) PS1, (iii) PS1 knockout mice, and (iv) wt mice in which PS1 gene expression was knocked down by antisense treatment. We found that primary neurons overexpressing mutated PS1 showed an increased vulnerability to both excitotoxic and hypoxic-hypoglycemic damage when compared with neurons obtained from either mice overexpressing human wt PS1 or in wt mice. In addition, reduced excitotoxic damage was obtained in neurons in which PS1 expression was absent or diminished. Data obtained in in vivo experimental models of excitotoxicity partially supported the in vitro observations. Accelerated neuronal death was demonstrated in the hippocampus of mice overexpressing mutated PS1 after peripheral administration of kainic acid in comparison with wt animals. However, measurement of the infarct volume after middle cerebral artery occlusion did not show significant difference between the two animal groups. The results altogether suggest that expression of FAD-linked PS1 variants increases the vulnerability of neurons to a specific type of damage in which excitotoxicity plays a relevant role. In addition, they support the view that reduction of endogenous PS1 expression results in neuroprotection.
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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.