Aging cell, 2018-06, Vol.17 (3), p.e12754-n/a
2018
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- Autor(en) / Beteiligte
- Titel
- nNOS–CAPON interaction mediates amyloid‐β‐induced neurotoxicity, especially in the early stages
- Ist Teil von
- Aging cell, 2018-06, Vol.17 (3), p.e12754-n/a
- Ort / Verlag
- England: John Wiley & Sons, Inc
- Erscheinungsjahr
- 2018
- Quelle
- Wiley-Blackwell Journals
- Beschreibungen/Notizen
- Summary In neurons, increased protein–protein interactions between neuronal nitric oxide synthase (nNOS) and its carboxy‐terminal PDZ ligand (CAPON) contribute to excitotoxicity and abnormal dendritic spine development, both of which are involved in the development of Alzheimer's disease. In models of Alzheimer's disease, increased nNOS–CAPON interaction was detected after treatment with amyloid‐β in vitro, and a similar change was found in the hippocampus of APP/PS1 mice (a transgenic mouse model of Alzheimer's disease), compared with age‐matched background mice in vivo. After blocking the nNOS–CAPON interaction, memory was rescued in 4‐month‐old APP/PS1 mice, and dendritic impairments were ameliorated both in vivo and in vitro. Furthermore, we demonstrated that S‐nitrosylation of Dexras1 and inhibition of the ERK–CREB–BDNF pathway might be downstream of the nNOS–CAPON interaction.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1474-9718eISSN: 1474-9726DOI: 10.1111/acel.12754Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5946066
- Format
- –
- Schlagworte
- Adaptor Proteins, Signal Transducing - metabolism, Alzheimer Disease - genetics, Alzheimer Disease - metabolism, Alzheimer Disease - pathology, Alzheimer's disease, Amyloid, Amyloid beta-Peptides - metabolism, Amyloid beta-Peptides - toxicity, amyloid‐β, Animal models, Animals, Brain-derived neurotrophic factor, Cells, Cultured, Comparative analysis, Cyclic AMP response element-binding protein, Dendritic spines, Development and progression, Dexras1, Disease Models, Animal, ERK–CREB–BDNF, Excitotoxicity, Genetic engineering, Hippocampus - drug effects, Hippocampus - metabolism, Hippocampus - pathology, Male, Mice, Mice, Transgenic, Neurodegenerative diseases, Neurons, Neurophysiology, Neurotoxicity, Neurotoxicity Syndromes - genetics, Neurotoxicity Syndromes - metabolism, Neurotoxicity Syndromes - pathology, Nitric oxide, Nitric Oxide Synthase Type I - metabolism, Nitric-oxide synthase, nNOS–CAPON interaction, Original, Peptide Fragments - metabolism, Peptide Fragments - toxicity, Presenilin 1, Protein interaction, Rodents, S‐nitrosylation, Transgenic mice