Molecular Neurobiology

, Volume 56, Issue 10, pp 6673–6702 | Cite as

The Neuroprotective Role of the GM1 Oligosaccharide, II3Neu5Ac-Gg4, in Neuroblastoma Cells

  • Elena ChiricozziEmail author
  • Margherita Maggioni
  • Erika di Biase
  • Giulia Lunghi
  • Maria Fazzari
  • Nicoletta Loberto
  • Maffioli Elisa
  • Francesca Grassi Scalvini
  • Gabriella Tedeschi
  • Sandro SonninoEmail author


Recently, we demonstrated that the GM1 oligosaccharide, II3Neu5Ac-Gg4 (OligoGM1), administered to cultured murine Neuro2a neuroblastoma cells interacts with the NGF receptor TrkA, leading to the activation of the ERK1/2 downstream pathway and to cell differentiation. To understand how the activation of the TrkA pathway is able to trigger key biochemical signaling, we performed a proteomic analysis on Neuro2a cells treated with 50 μM OligoGM1 for 24 h. Over 3000 proteins were identified. Among these, 324 proteins were exclusively expressed in OligoGM1-treated cells. Interestingly, several proteins expressed only in OligoGM1-treated cells are involved in biochemical mechanisms with a neuroprotective potential, reflecting the GM1 neuroprotective effect. In addition, we found that the exogenous administration of OligoGM1 reduced the cellular oxidative stress in Neuro2a cells and conferred protection against MPTP neurotoxicity. These results confirm and reinforce the idea that the molecular mechanisms underlying the GM1 neurotrophic and neuroprotective effects depend on its oligosaccharide chain, suggesting the activation of a positive signaling starting at plasma membrane level.


GM1 ganglioside GM1 oligosaccharide chain TrkA neurotrophin receptor Plasma membrane signaling Neuroprotection Shotgun label-free proteomic 


Ganglioside nomenclature

is in accordance with IUPAC-IUBB recommendations [1]


II3Neu5Ac-Gg4Cer, β-Gal-(1-3)-β-GalNAc-(1-4)-[α-Neu5Ac-(2-3)]-β-Gal-(1-4)-β-Glc-Cer


GM1 oligosaccharide, II3Neu5Ac-Gg4




Dulbecco’s modified Eagle’s medium


Extracellular signal-regulated protein kinases 1 and 2


Fetal bovine serum


High-performance silica gel thin-layer chromatography


Ingenuity Pathway Analysis


Mitogen-activated protein kinase




1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride


Mass spectrometry


Neuro2a cells


Nerve growth factor


Phosphate-buffered saline


Phosphorylated ERK1/2


Phosphorylated TrkA


Plasma membrane


Polyvinylidene difluoride


Retinoic acid


Reactive oxygen species


Research resource identifiers


Neurotrophin tyrosine kinase receptor


Tyrosine 490


Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Supplementary material

12035_2019_1556_MOESM1_ESM.docx (15.6 mb)
ESM 1 (DOCX 16006 kb)


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Authors and Affiliations

  1. 1.Department of Medical Biotechnology and Translational MedicineUniversity of MilanSegrateItaly
  2. 2.Department of Veterinary MedicineUniversity of MilanMilanItaly
  3. 3.Fondazione UnimiMilanItaly

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