2. Academic Validation
  3. ICA1 affects APP processing through the PICK1-PKCα signaling pathway

ICA1 affects APP processing through the PICK1-PKCα signaling pathway

  • CNS Neurosci Ther. 2024 Jun;30(6):e14754. doi: 10.1111/cns.14754.
Liangye Ji 1,  ZiJun Meng 1,  Xiangjun Dong 1,  Qunxian Wang 1,  Yanshuang Jiang 1,  Jie Zhang 1,  Dongjie Hu 1,  Shipeng Guo 1,  Weihui Zhou 1,  Weihong Song 1 2 3
Affiliations

Affiliations

  • 1 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.
  • 2 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.
  • 3 Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), Wenzhou, China.
PMID: 38884369 DOI: 10.1111/cns.14754
Abstract

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 PKCα protein levels and phosphorylation.

Conclusion: 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.

Keywords

APP; Alzheimer's disease; ICA1; PICK1; PKCα.

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