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Structural Codes of Sphingolipids and Their Involvement in Diseases

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Biochemistry".

Deadline for manuscript submissions: 30 November 2025 | Viewed by 818

Special Issue Editors


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Guest Editor
Department of Medical Biotechnology and Translational Medicine, University of Milano, 20054 Milano, Italy
Interests: gangliosides; Parkinson’s disease; mebrane organization; complex lipids; sphingosine; ceramide
Special Issues, Collections and Topics in MDPI journals

E-Mail Website
Guest Editor
Department of Medical Biotechnology and Translational Medicine, University of Milan, Milan, Italy
Interests: glycosphingolipids; gangliosides; GM1; GM1 oligosaccharide; plasma membrane signaling; neuronal disease; Parkinson’s disease
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Sphingolipids are complex membrane components and are characterized by a great diversity of their structure. They show a wide range of amphiphilic characters, ranging from very hydrophobic to very hydrophilic molecules. Both of the two moieties, the hydrophobic tail and the hydrophilic head, are recognized by specific protein sequences of amino acids that allow the formation of sphingolipid-protein complexes necessary for metabolic processes instrumental for the correct life of cells. The structural diversity of sphingolipids allows the formation of multiple sphingolipid-protein complexes instrumental for a variety of cellular processes. Derailment from the correct synthesis or catabolism of sphingolipids leads to an altered membrane composition followed by incorrect or impossible interaction processes between sphingolipids and proteins, lipid transporters, or membrane receptors. As a result, an altered physiology of the cell follows with the onset of serious diseases.

Contributions to this Special Issue should focus on the latest advances in sphingolipid biophysics, biochemistry, and cell and molecular biology instrumental for the understanding of some aspects of neuronal development, cancer, host–pathogen interactions, and, with a special emphasis on how these molecules disease and neurodegeneration.

Prof. Dr. Sandro Sonnino
Dr. Elena Chiricozzi
Guest Editors

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Keywords

  • sphingolipids
  • sphingolipid hydrophilic head
  • sphingolipid hydrophobic tail
  • sphingolipid signalling
  • sphingolipid diseases

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Published Papers (1 paper)

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Research

12 pages, 948 KB  
Article
GM1 Oligosaccharide Modulates Microglial Activation and α-Synuclein Clearance in a Human In Vitro Model
by Giulia Lunghi, Carola Pedroli, Maria Grazia Ciampa, Laura Mauri, Laura Rouvière, Alexandre Henriques, Noelle Callizot, Benedetta Savino and Maria Fazzari
Int. J. Mol. Sci. 2025, 26(15), 7634; https://doi.org/10.3390/ijms26157634 - 7 Aug 2025
Viewed by 571
Abstract
Neuroinflammation driven by microglial activation and α-synuclein (αSyn) aggregation is one of the central features driving Parkinson’s disease (PD) pathogenesis. GM1 ganglioside’s oligosaccharide moiety (OligoGM1) has shown neuroprotective potential in PD neuronal models, but its direct effects on inflammation remain poorly defined. This [...] Read more.
Neuroinflammation driven by microglial activation and α-synuclein (αSyn) aggregation is one of the central features driving Parkinson’s disease (PD) pathogenesis. GM1 ganglioside’s oligosaccharide moiety (OligoGM1) has shown neuroprotective potential in PD neuronal models, but its direct effects on inflammation remain poorly defined. This study investigated the ability of OligoGM1 to modulate microglial activation and αSyn handling in a human in vitro model. Human embryonic microglial (HMC3) cells were exposed to αSyn pre-formed fibrils (PFFs) in the presence or absence of OligoGM1. Microglial activation markers, intracellular αSyn accumulation, and cytokine release were assessed by immunofluorescence and ELISA. OligoGM1 had no effect on microglial morphology or cytokine release under basal conditions. Upon αSyn challenge, cells exhibited increased amounts of ionized calcium-binding adaptor molecule 1 (Iba1), triggered receptor expressed on myeloid cells 2 (TREM2), elevated αSyn accumulation, and secreted pro-inflammatory cytokines. OligoGM1 pre-treatment significantly reduced the number and area of Iba1(+) cells, the intracellular αSyn burden in TREM2(+) microglia, and the release of interleukin 6 (IL-6). OligoGM1 selectively attenuated αSyn-induced microglial activation and enhanced αSyn clearance without compromising basal immune function. These findings confirm and support the potential of OligoGM1 as a multitarget therapeutic candidate for PD that is capable of modulating glial reactivity and neuroinflammatory responses. Full article
(This article belongs to the Special Issue Structural Codes of Sphingolipids and Their Involvement in Diseases)
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