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.

The Neuroprotective Role of the GM1 Oligosaccharide, II3Neu5Ac-Gg4, in Neuroblastoma Cells / E. Chiricozzi, M. Maggioni, E. di Biase, G. Lunghi, M. Fazzari, N. Loberto, E.M. Maffioli, F.G. Scalvini, G. Tedeschi, S. Sonnino. - In: MOLECULAR NEUROBIOLOGY. - ISSN 0893-7648. - 56:10(2019 Oct 01), pp. 6673-6702. [10.1007/s12035-019-1556-8]

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

E. Chiricozzi
Primo
;
M. Maggioni
Secondo
;
E. di Biase;G. Lunghi;M. Fazzari;N. Loberto;E.M. Maffioli;F.G. Scalvini;G. Tedeschi
Penultimo
;
S. Sonnino
Ultimo
2019-10-01

Abstract

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; Neuroprotection; Plasma membrane signaling; Shotgun label-free proteomic; TrkA neurotrophin receptor
Settore BIO/10 - Biochimica
Dipartimenti di Eccellenza 2018-2022 - Dipartimento di FILOSOFIA
26-mar-2019
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/636080
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