Extended coverage of human serum glycosphingolipidome by 4D-RP-LC TIMS-PASEF unravels association with Parkinson’s disease

Huong Giang Vo, Gabriel Gonzalez-Escamilla, Daniela Mirzac, Lilia Rotaru, Damian Herz, Sergiu Groppa and Laura Bindila ()
Additional contact information
Huong Giang Vo: University Medical Center
Gabriel Gonzalez-Escamilla: University Medical Center
Daniela Mirzac: University Medical Center
Lilia Rotaru: Diomid Gherman Institute of Neurology and Neurosurgery
Damian Herz: University Medical Center
Sergiu Groppa: University Medical Center
Laura Bindila: University Medical Center

Nature Communications, 2025, vol. 16, issue 1, 1-22

Abstract: Abstract Glycosphingolipids (GSLs) are important targets in immune, infectious, lysosomal storage diseases, cancer, and neurodegenerative diseases. Circulatory GSLs profiling in clinical samples is restricted by the lack of mid- and high-throughput analytical methods and deep coverage of long-chain sialylated glycosphingolipidome. We present a 4-dimensional (4D)-glycosphingolipidomics platform for routine glycosphingolipidome profiling encompassing: extraction and fractionation of sialylated GSLs with 3 to 15 monosaccharides, neutral GSLs and sulfatides; µL-flow reversed-phase LC-TIMS-PASEF MS analysis; semi-quantification strategy adapted for fractionated glycosphingolipidome, and referential CCS, RT, and m/z values for GSLs annotation. 4D-glycosphingolipidomics of human serum reveals a high structural heterogeneity, amounting to 376 GSLs: 159 GSLs of ganglio- and neolacto-series, 145 neutral GSLs and 72 sulfatides. Here we demonstrate the platform’s utility for clinical profiling of Parkinson’s disease (PD) sera. 41 neolacto- and ganglio-species discriminate PD patients from controls and 14 GSLs differentiate sex subgroups, laying the foundation for further functional GSL studies with PD.

Date: 2025
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-025-59755-6 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-59755-6

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-025-59755-6

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().