Open AccessnNOS – CAPON interaction mediates amyloid‐β‐induced neurotoxicity, especially in the early stages
Author(s) -
Zhang Yu,
Zhu Zhu,
Liang HaiYing,
Zhang Lei,
Zhou QiGang,
Ni HuanYu,
Luo ChunXia,
Zhu DongYa
Publication year - 2018
Publication title -
aging cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.103
H-Index - 140
eISSN - 1474-9726
pISSN - 1474-9718
DOI - 10.1111/acel.12754
Subject(s) - capon , excitotoxicity , biology , neurotoxicity , genetically modified mouse , in vivo , pdz domain , hippocampus , nitric oxide , neuroscience , microbiology and biotechnology , glutamate receptor , receptor , transgene , medicine , endocrinology , biochemistry , toxicity , genetics , beamforming , statistics , mathematics , gene
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 / PS 1 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 / PS 1 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.