Department of Pediatric Research Institute Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, China International Science and Technology Cooperation base of Child development and Critical Disorders, Chongqing Key Laboratory of Child Neurodevelopment and Cognitive Disorders, Children's Hospital of Chongqing Medical University, Chongqing, China.
The Second Affiliated Hospital and Yuying Children's Hospital, Institute of Aging, Key Laboratory of Alzheimer's Disease of Zhejiang Province, Wenzhou Medical University, Wenzhou, China.
CNS Neurosci Ther. 2024 Jun;30(6):e14754. doi: 10.1111/cns.14754.
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.
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 PKCα protein levels and phosphorylation.
Our results demonstrated that ICA1 shifts APP processing to non-amyloid pathways by regulating the PICK1-PKCα signaling pathway. Thus, this study suggests that ICA1 is a novel target for the treatment of AD.
胰岛细胞自身抗原 1（ICA1）参与自身免疫性疾病，并且可能作为神经递质影响突触可塑性。与阿尔茨海默病（AD）相关的数据库显示，AD 患者的 ICA1 表达降低。然而，ICA1 在 AD 中的作用仍不清楚。在这里，我们报告在 AD 患者和 AD 小鼠模型的大脑中 ICA1 的表达降低。
ICA1 增加了淀粉样前体蛋白（APP）、解整合素和金属蛋白酶 10（ADAM10）和解整合素和金属蛋白酶 17（ADAM17）的表达，但不影响蛋白半衰期或 mRNA 水平。转录组测序分析显示 ICA1 调节 G 蛋白偶联受体信号通路。ICA1 的过表达增加了 PKCα 蛋白水平和磷酸化。
我们的结果表明，ICA1 通过调节 PICK1-PKCα 信号通路将 APP 加工转移到非淀粉样途径。因此，本研究表明 ICA1 是治疗 AD 的一个新靶点。
Zotero 插件
