Work

CCNE1 Exerts a Protective Effect on Parkinson's Disease by Regulating Ferroptosis‐Related Proteins

Year: 2025

Type: article

Abstract: BACKGROUND: The pathogenesis of Parkinson's disease (PD) is closely linked to ferroptosis, yet the mechanism by which ferroptosis-related proteins modulate PD risk through genetic variations remains unclear. METHODS: We performed two-sample Mendelian randomization (MR) analyses using protein quantitative trait loci (pQTLs) from the UKB-PPP and deCODE studies as instrumental variables, combined with PD genome-wide association study (GWAS) data. The inverse variance weighting (IVW) method served as the primary analytical approach to identify PD-associated proteins. To assess the role of ferroptosis-related proteins in PD, a two-step MR mediation analysis was conducted, followed by multiple sensitivity analyses. Transcriptomic datasets were analyzed to confirm the differential expression of genes encoding prioritized proteins. Publicly available single-cell RNA sequencing data were utilized to investigate cell-type-specific expression patterns and functional pathways of key proteins. RESULTS: ), with CCNE1's differential expression further validated in transcriptomic datasets. Single-cell analysis demonstrated that CCNE1 and PARP16 are specifically highly expressed in neurons (p < 0.05), with neurons being significantly enriched in neural survival and synaptic plasticity pathways. The cell interaction network revealed that neurons specifically communicate with astrocytes via the NRG3-ERBB4 pathway. CONCLUSION: This study provides the first molecular insight into how CCNE1 exerts neuroprotective effects through the regulation of the ferroptosis key protein PARP16, offering a novel perspective for PD mechanism research.

Source: Brain and Behavior

DOI: 10.1002/brb3.71110

Authors: Jia Fu, Jing Zhao, Na Mi, Chao Zhang, Yali Zhang, Lifen Yao

Institutions: Harbin Medical University, Chifeng Municipal Hospital, First Affiliated Hospital of Harbin Medical University

Language: English

Topic: Parkinson's Disease Mechanisms and Treatments

Subfield: Neurology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,630