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NNOS-CAPON interaction mediates amyloid-?-induced neurotoxicity, especially in the early stages.

ABSTRACT: 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-? 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.

SUBMITTER: Zhang Y

PROVIDER: S-EPMC5946066 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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nNOS-CAPON interaction mediates amyloid-β-induced neurotoxicity, especially in the early stages.

Zhang Yu Y Zhu Zhu Z Liang Hai-Ying HY Zhang Lei L Zhou Qi-Gang QG Ni Huan-Yu HY Luo Chun-Xia CX Zhu Dong-Ya DY

Aging cell 20180325 3

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 Al ...[more]

PMID: 29577585

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