ArticleThe Journal of biological chemistry2012
Conditional deletion of Notch1 and Notch2 genes in excitatory neurons of postnatal forebrain does not cause neurodegeneration or reduction of Notch mRNAs and proteins.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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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.
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20 citing papers in PubMed, 31 citations in OpenAlex.
- Lipophorin receptors genetically modulate neurodegeneration caused by reduction of Psn expression in the aging Drosophila brain.Genetics · 2024Article
- The Regulation of Astrocytic Glutamate Transporters in Health and Neurodegenerative Diseases.International journal of molecular sciences · 2020Review
- Cell-autonomous role of Presenilin in age-dependent survival of cortical interneurons.Molecular neurodegeneration · 2020Article
- Exploring the Role of PSEN Mutations in the Pathogenesis of Alzheimer's Disease.Neurotoxicity research · 2020Review
- Post-Developmental Roles of Notch Signaling in the Nervous System.Biomolecules · 2020Review
- Adult hippocampal neurogenesis occurs in the absence of Presenilin 1 and Presenilin 2.Scientific reports · 2018Article
- Inactivation of γ-secretases leads to accumulation of substrates and non-Alzheimer neurodegeneration.EMBO molecular medicine · 2017Article
- Article
- Presenilin-1 mutations and Alzheimer's disease.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- A novel non-canonical Notch signaling regulates expression of synaptic vesicle proteins in excitatory neurons.Scientific reports · 2016Article
- Article
- Mesenchymal deficiency of Notch1 attenuates bleomycin-induced pulmonary fibrosis.The American journal of pathology · 2015Article
- Notch Intracellular Domain (NICD) Suppresses Long-Term Memory Formation in Adult Drosophila Flies.Cellular and molecular neurobiology · 2015Article
- Notch is required in adult Drosophila sensory neurons for morphological and functional plasticity of the olfactory circuit.PLoS genetics · 2015Article
- Synaptic function of nicastrin in hippocampal neurons.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
- Function and dysfunction of presenilin.Neuro-degenerative diseases · 2014Review
- Presenilin 2 influences miR146 level and activity in microglia.Journal of neurochemistry · 2013Article
- Expression of notch proteins in pyramidal neurons in vivo.The Journal of biological chemistry · 2012Article
- Loss of RBPj in postnatal excitatory neurons does not cause neurodegeneration or memory impairments in aged mice.PloS one · 2012Article
- History and progress of hypotheses and clinical trials for Alzheimer's disease.Signal transduction and targeted therapyReview
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7 authors at 3 institutions in 2 countries.
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Abstract
Activation of Notch signaling requires intramembranous cleavage by γ-secretase to release the intracellular domain. We previously demonstrated that presenilin and nicastrin, components of the γ-secretase complex, are required for neuronal survival in the adult cerebral cortex. Here we investigate whether Notch1 and/or Notch2 are functional targets of presenilin/γ-secretase in promoting survival of excitatory neurons in the adult cerebral cortex by generating Notch1, Notch2, and Notch1/Notch2 conditional knock-out (cKO) mice. Unexpectedly, we did not detect any neuronal degeneration in the adult cerebral cortex of these Notch cKO mice up to ∼2 years of age, whereas conditional inactivation of presenilin or nicastrin using the same αCaMKII-Cre transgenic mouse caused progressive, striking neuronal loss beginning at 4 months of age. More surprisingly, we failed to detect any reduction of Notch1 and Notch2 mRNAs and proteins in the cerebral cortex of Notch1 and Notch2 cKO mice, respectively, even though Cre-mediated genomic deletion of the floxed Notch1 and Notch2 exons clearly took place in the cerebral cortex of these cKO mice. Furthermore, introduction of Cre recombinase into primary cortical cultures prepared from postnatal floxed Notch1/Notch2 pups, where Notch1 and Notch2 are highly expressed, completely eliminated their expression, indicating that the floxed Notch1 and Notch2 alleles can be efficiently inactivated in the presence of Cre. Together, these results demonstrate that Notch1 and Notch2 are not involved in the age-related neurodegeneration caused by loss of presenilin or γ-secretase and suggest that there is no detectable expression of Notch1 and Notch2 in pyramidal neurons of the adult cerebral cortex.
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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.