Caspase-1/IL-1β represses membrane transport of GluA1 by inhibiting the interaction between Stargazin and GluA1 in Alzheimer’s disease
In: Molecular Medicine Molecular Medicine, Jg. 27 (2021), Heft 1, S. 1-11
Online
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Zugriff:
Background Alzheimer's disease is a neurodegenerative disease. Previous study has reported that caspase-1/IL-1β is closely associated with Alzheimer's disease. However, the biological role of caspase-1/IL-1β in Alzheimer's disease has not been fully elucidated. This study aimed to explore the mechanism of action of caspase-1/IL-1β in Alzheimer's disease. Methods Mouse hippocampal neurones were treated with Aβ1-42 to induce Alzheimer's disease cell model. APP/PS1 mice and Aβ1-42-induced hippocampal neurones were treated with AC-YVAD-CMK (caspase-1 inhibitor). Spatial learning and memory ability of mice were detected by morris water maze. Flow cytometry, TUNEL staining, Thioflavin S staining and immunohistochemistry were performed to examine apoptosis and senile plaque deposition. Enzyme linked immunosorbent assay and western blot were performed to assess the levels of protein or cytokines. Co-Immunoprecipitation was performed to verify the interaction between Stargazin and GluA1. Results AC-YVAD-CMK treatment improved spatial learning and memory ability and reduced senile plaque deposition of APP/PS1 mice. Moreover, AC-YVAD-CMK promoted membrane transport of GluA1 in APP/PS1 mice. In vitro, Aβ1-42-induced hippocampal neurones exhibited an increase in apoptosis and a decrease in the membrane transport of GluA1, which was abolished by AC-YVAD-CMK treatment. In addition, Stargazin interacted with GluA1, which was repressed by caspase-1. Caspase-1/IL-1β inhibited membrane transport of GluA1 by inhibiting the interaction between Stargazin and GluA1. Conclusions Our data demonstrate that caspase-1/IL-1β represses membrane transport of GluA1 by inhibiting the interaction between Stargazin in Alzheimer's disease. Thus, caspase-1/IL-1β may be a target for Alzheimer's disease treatment.
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Caspase-1/IL-1β represses membrane transport of GluA1 by inhibiting the interaction between Stargazin and GluA1 in Alzheimer’s disease
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Autor/in / Beteiligte Person: | Wu, Han-Jun ; Xu, Lijun ; Wang, Wei ; Liu, Xu ; Xie, Yuqin ; Gu, Xun-Hu |
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Zeitschrift: | Molecular Medicine Molecular Medicine, Jg. 27 (2021), Heft 1, S. 1-11 |
Veröffentlichung: | Springer Science and Business Media LLC, 2021 |
Medientyp: | unknown |
ISSN: | 1528-3658 (print) ; 1076-1551 (print) |
DOI: | 10.1186/s10020-021-00273-8 |
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