The roles of RACK1 in the pathogenesis of Alzheimer's disease

• Published in: Journal of biomedical research 2024-02, Vol.38 (2), p.137-148
• Main Authors: He, Wenting, Shi, Xiuyu, Dong, Zhifang
• Format: Article
• Language: English
• Subjects: Review
• ISSN: 1674-8301; 1674-8301; 2352-4685
• DOI: 10.7555/JBR.37.20220259

The receptor for activated C kinase 1 (RACK1) is a protein that plays a crucial role in various signaling pathways and is involved in the pathogenesis of Alzheimer's disease (AD), a prevalent neurodegenerative disease. RACK1 is highly expressed in neuronal cells of the central nervous system and regulates the pathogenesis of AD. Specifically, RACK1 is involved in regulation of the amyloid-β precursor protein processing through α- or β-secretase by binding to different protein kinase C isoforms. Additionally, RACK1 promotes synaptogenesis and synaptic plasticity by inhibiting N-methyl-D-aspartate receptors and activating gamma-aminobutyric acid A receptors, thereby preventing neuronal excitotoxicity. RACK1 also assembles inflammasomes that are involved in various neuroinflammatory pathways, such as nuclear factor-kappa B, tumor necrosis factor-alpha, and NOD-like receptor family pyrin domain-containing 3 pathways. The potential to design therapeutics that block amyloid-β accumulation and inflammation or precisely regulate synaptic plasticity represents an attractive therapeutic strategy, in which RACK1 is a potential target. In this review, we summarize the contribution of RACK1 to the pathogenesis of AD and its potential as a therapeutic target.