Bibliographic Details
| Title: |
Lysophosphatidylcholine promoting α-Synuclein aggregation in Parkinson’s disease: disrupting GCase glycosylation and lysosomal α-Synuclein degradation |
| Authors: |
Chunyan Mu, Kaiquan Shao, Mingyu Su, Yurong Guo, Yuxiang Qiu, Ruiao Sun, Sihan Sun, Yaoyu Sun, Chenkai Liu, Wei Wang, Xiaoling Qin, Chuanxi Tang |
| Source: |
npj Parkinson's Disease, Vol 11, Iss 1, Pp 1-20 (2025) |
| Publisher Information: |
Nature Portfolio, 2025. |
| Publication Year: |
2025 |
| Collection: |
LCC:Neurology. Diseases of the nervous system |
| Subject Terms: |
Neurology. Diseases of the nervous system, RC346-429 |
| More Details: |
Abstract In Parkinson’s Disease (PD), elevated serum lysophosphatidylcholine (LPC) levels correlate with disease progression. However, the mechanisms by which abnormal LPC elevation contributes to PD-related neurotoxicity remain poorly understood. This study aims to investigate the pathogenic role of LPC in dopaminergic neuronal damage and elucidates its underlying mechanisms. Our results showed LPC induces α-synuclein aggregation, exacerbating cognitive dysfunction. LPC activates Cleaved-Caspase3 via the orphan receptor GPR35-ERK signaling pathway, inhibits GRASP65 expression, and disrupts the polarized structure of the Golgi apparatus. This disruption impairs glycosylation and function of glucocerebrosidase (GCase), preventing its transport to lysosomes and leading to glucosylceramide (GlcCer) accumulation, a scaffold for α-synuclein aggregation. LPC also disrupts the autophagolysosomal pathway and lysosomal acidification, exacerbating toxic α-synuclein accumulation. Restoring GCase glycosylation, limiting GlcCer synthesis, or blocking ERK signaling mitigates these effects. This study highlights LPC’s role in promoting α-synuclein aggregation and autophagolysosomal dysfunction, advancing our understanding of PD pathology. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
2373-8057 |
| Relation: |
https://doaj.org/toc/2373-8057 |
| DOI: |
10.1038/s41531-025-00902-7 |
| Access URL: |
https://doaj.org/article/1f10c1a22b66453794960e9cde63fb36 |
| Accession Number: |
edsdoj.1f10c1a22b66453794960e9cde63fb36 |
| Database: |
Directory of Open Access Journals |
