Year: 2025
Type: article
Abstract: Parkinson's disease (PD) is a neurodegenerative disorder characterized by the loss of dopaminergic neurons and the abnormal aggregation of α-synuclein (α-Syn), involving complex regulatory networks where the roles and mechanisms of circular RNAs (circRNAs) remain underexplored. Through RNA sequencing analysis, we identified significant upregulation of circ_0005654 (derived from the PRDM5 gene) in PD patients. Functional studies demonstrated that circ_0005654 overexpression promotes α-Syn accumulation through a dual regulatory mechanism: (1) direct enhancement of its transcriptional/translational activation of α-Syn and (2) indirect suppression of autophagic clearance via miR-588 sequestration-mediated inhibition of the p62-dependent autophagy pathway. Specifically, circ_0005654 functions as a molecular sponge for miR-588, thereby coordinately enhancing α-Syn synthesis while impairing its degradation. This study not only establishes the functional role of circRNAs in PD pathogenesis but also elucidates circ_0005654 as a promising therapeutic candidate for targeted modulation of α-Syn aggregation.
Source: The FASEB Journal
Authors: Jiang Lei, Jiajia Liao, Yingyao Liu, Yao Liu, Wenxuan He, Qinxin Zhang, Yuefei Shen, Jin Wang, Pingyi Xu, Yulan Tang, Lu Gan, Yousheng Xiao
Language: English
Topic: Circular RNAs in diseases
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: bronze
OpenAlex ID: W4410900280