ICA1 affects APP processing through the PICK1-PKCα signaling pathway

作者全名：Ji, Liangye; Meng, Zijun; Dong, Xiangjun; Wang, Qunxian; Jiang, Yanshuang; Zhang, Jie; Hu, Dongjie; Guo, Shipeng; Zhou, Weihui; Song, Weihong

作者地址：[Ji, Liangye; Meng, Zijun; Dong, Xiangjun; Wang, Qunxian; Jiang, Yanshuang; Zhang, Jie; Hu, Dongjie; Guo, Shipeng; Zhou, Weihui; Song, Weihong] Chongqing Med Univ, Chongqing Med Univ, Natl Clin Res Ctr Child Hlth & Disorders, China Int Sci & Technol Cooperat Base Child Dev &, Chongqing, Peoples R China; [Song, Weihong] Wenzhou Med Univ, Affiliated Hosp 2, Inst Aging, Key Lab Alzheimers Dis Zhejiang Prov, Wenzhou, Peoples R China; [Song, Weihong] Wenzhou Med Univ, Yuying Childrens Hosp, Inst Aging, Key Lab Alzheimers Dis Zhejiang Prov, Wenzhou, Peoples R China; [Song, Weihong] Oujiang Lab, Zhejiang Lab Regenerat Med Vis & Brain Hlth, Wenzhou, Peoples R China

通信作者：Meng, ZJ; Zhou, WH; Song, WH (通讯作者)，Chongqing Med Univ, Chongqing Med Univ, Natl Clin Res Ctr Child Hlth & Disorders, China Int Sci & Technol Cooperat Base Child Dev &, Chongqing, Peoples R China.

来源：CNS NEUROSCIENCE & THERAPEUTICS

ESI学科分类：PHARMACOLOGY & TOXICOLOGY

WOS号：WOS:001250572700001

JCR分区：Q1

影响因子：4.8

年份：2024

卷号：30

期号：6

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结束页：　

文献类型：Article

关键词：Alzheimer's disease; APP; ICA1; PICK1; PKC alpha

摘要：Aims: Islet cell autoantigen 1 (ICA1) is involved in autoimmune diseases and may affect synaptic plasticity as a neurotransmitter. Databases related to Alzheimer's disease (AD) have shown decreased ICA1 expression in patients with AD. However, the role of ICA1 in AD remains unclear. Here, we report that ICA1 expression is decreased in the brains of patients with AD and an AD mouse model. Results: The ICA1 increased the expression of amyloid precursor protein (APP), disintegrin and metalloprotease 10 (ADAM10), and disintegrin and metalloprotease 17 (ADAM17), but did not affect protein half-life or mRNA levels. Transcriptome sequencing analysis showed that ICA1 regulates the G protein-coupled receptor signaling pathway. The overexpression of ICA1 increased PKC alpha protein levels and phosphorylation. Conclusion: Our results demonstrated that ICA1 shifts APP processing to non-amyloid pathways by regulating the PICK1-PKC alpha signaling pathway. Thus, this study suggests that ICA1 is a novel target for the treatment of AD.

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