In light of its neurotrophic and neuroprotective properties, GM1 ganglioside has been considered as a master regulator of the nervous system. Recently, we demonstrated in a mouse neuroblastoma cell line N2a that the oligosaccharide portion of GM1 (OligoGM1) is responsible for the ability of GM1 to induce neuritogenesis by the activation of the TrkA-MAPK pathway. This means that the specific role of GM1 in neuronal differentiation is determined by a direct interaction between its oligosaccharide portion and specific proteins expressed on the plasma membrane. In order to understand if the exogenous administration of OligoGM1 and the resulting activation of TrkA pathway is able to trigger crucial biochemical signaling, we performed a proteomic analysis on N2a cells treated with 50 µM OligoGM1 for 24 hours. The analysis led to the identification and quantification of 744 proteins; 324 proteins were identified only in OligoGM1-treated cells. Interestingly, the OligoGM1-only proteins are mainly involved in biochemical mechanisms, many of which offer neuroprotective potential reflecting the GM1 neuroprotective effect. To confirm that the neuroprotective effect of GM1 is due to its oligosaccharide portion, OligoGM1-treated N2a cells were administered with MPTP for 48 hours. We found that MPTP-induced mortality was reduced by 50% in OligoGM1-treated cells respect to untreated ones. Furthermore, we saw that the administration to N2a cells of dichlorobenzamil (DCB), a potent inhibitor of the Na+-Ca2+ antiporter, which results in elevating intracellular Ca2+, is responsible for cell death after 24-hour exposure. In presence of 50 µM OligoGM1 the DCB-cell mortality is definitely reduced, suggesting that the modulation of Ca2+ flux might be one mechanism in the neuroprotective effect due to exogenous administration of OligoGM1. Our results suggest that the molecular mechanisms underlying the neuroprotection effects induced by GM1 depend on its oligosaccharide chain.
GM1 neuroprotective properties are related to GM1 oligosaccharide / G. Lunghi, M. Maggioni, E. Di Biase, G. Tedeschi, E. Maffioli, F. Grassi Scalvini, E. Chiricozzi, S. Sonnino. - In: FEBS OPENBIO. - ISSN 2211-5463. - 8:suppl. 1(2018 Jul), pp. 368-368. ((Intervento presentato al 43. convegno FEBS Congress: Biochemistry forever tenutosi a Prague (Czech Republic) nel 2018.
|Titolo:||GM1 neuroprotective properties are related to GM1 oligosaccharide|
|Settore Scientifico Disciplinare:||Settore BIO/10 - Biochimica|
|Data di pubblicazione:||lug-2018|
|Appare nelle tipologie:||01 - Articolo su periodico|
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