GM1 ganglioside exerts protective effects against glutamate‐excitotoxicity via its oligosaccharide in wild‐type and amyotrophic lateral sclerosis motor neurons

Alterations in glycosphingolipid metabolism have been linked to the pathophysiological mechanisms of amyotrophic lateral sclerosis (ALS), a neurodegenerative disease affecting motor neurons. Accordingly, administration of GM1, a sialic acid‐containing glycosphingolipid, is protective against neurona...

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Main Authors: Giulia Lunghi, Erika Di Biase, Emma Veronica Carsana, Alexandre Henriques, Noelle Callizot, Laura Mauri, Maria Grazia Ciampa, Luigi Mari, Nicoletta Loberto, Massimo Aureli, Sandro Sonnino, Michael Spedding, Elena Chiricozzi, Maria Fazzari
Format: Article
Language:English
Published: Wiley 2023-12-01
Series:FEBS Open Bio
Subjects:
Online Access:https://doi.org/10.1002/2211-5463.13727
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author Giulia Lunghi
Erika Di Biase
Emma Veronica Carsana
Alexandre Henriques
Noelle Callizot
Laura Mauri
Maria Grazia Ciampa
Luigi Mari
Nicoletta Loberto
Massimo Aureli
Sandro Sonnino
Michael Spedding
Elena Chiricozzi
Maria Fazzari
author_facet Giulia Lunghi
Erika Di Biase
Emma Veronica Carsana
Alexandre Henriques
Noelle Callizot
Laura Mauri
Maria Grazia Ciampa
Luigi Mari
Nicoletta Loberto
Massimo Aureli
Sandro Sonnino
Michael Spedding
Elena Chiricozzi
Maria Fazzari
author_sort Giulia Lunghi
collection DOAJ
description Alterations in glycosphingolipid metabolism have been linked to the pathophysiological mechanisms of amyotrophic lateral sclerosis (ALS), a neurodegenerative disease affecting motor neurons. Accordingly, administration of GM1, a sialic acid‐containing glycosphingolipid, is protective against neuronal damage and supports neuronal homeostasis, with these effects mediated by its bioactive component, the oligosaccharide head (GM1‐OS). Here, we add new evidence to the therapeutic efficacy of GM1 in ALS: Its administration to WT and SOD1G93A motor neurons affected by glutamate‐induced excitotoxicity significantly increased neuronal survival and preserved neurite networks, counteracting intracellular protein accumulation and mitochondria impairment. Importantly, the GM1‐OS faithfully replicates GM1 activity, emphasizing that even in ALS the protective function of GM1 strictly depends on its pentasaccharide.
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spelling doaj.art-bc90ee2630b94cd7baec16a20f019b9f2023-12-06T13:08:18ZengWileyFEBS Open Bio2211-54632023-12-0113122324234110.1002/2211-5463.13727GM1 ganglioside exerts protective effects against glutamate‐excitotoxicity via its oligosaccharide in wild‐type and amyotrophic lateral sclerosis motor neuronsGiulia Lunghi0Erika Di Biase1Emma Veronica Carsana2Alexandre Henriques3Noelle Callizot4Laura Mauri5Maria Grazia Ciampa6Luigi Mari7Nicoletta Loberto8Massimo Aureli9Sandro Sonnino10Michael Spedding11Elena Chiricozzi12Maria Fazzari13Department of Medical Biotechnology and Translational Medicine University of Milano Segrate ItalyDepartment of Medical Biotechnology and Translational Medicine University of Milano Segrate ItalyDepartment of Medical Biotechnology and Translational Medicine University of Milano Segrate ItalyNeuro‐sys Gardanne FranceNeuro‐sys Gardanne FranceDepartment of Medical Biotechnology and Translational Medicine University of Milano Segrate ItalyDepartment of Medical Biotechnology and Translational Medicine University of Milano Segrate ItalyDepartment of Immunology St. Jude Children's Research Hospital Memphis TN USADepartment of Medical Biotechnology and Translational Medicine University of Milano Segrate ItalyDepartment of Medical Biotechnology and Translational Medicine University of Milano Segrate ItalyDepartment of Medical Biotechnology and Translational Medicine University of Milano Segrate ItalySpedding Research Solutions Le Vésinet FranceDepartment of Medical Biotechnology and Translational Medicine University of Milano Segrate ItalyDepartment of Medical Biotechnology and Translational Medicine University of Milano Segrate ItalyAlterations in glycosphingolipid metabolism have been linked to the pathophysiological mechanisms of amyotrophic lateral sclerosis (ALS), a neurodegenerative disease affecting motor neurons. Accordingly, administration of GM1, a sialic acid‐containing glycosphingolipid, is protective against neuronal damage and supports neuronal homeostasis, with these effects mediated by its bioactive component, the oligosaccharide head (GM1‐OS). Here, we add new evidence to the therapeutic efficacy of GM1 in ALS: Its administration to WT and SOD1G93A motor neurons affected by glutamate‐induced excitotoxicity significantly increased neuronal survival and preserved neurite networks, counteracting intracellular protein accumulation and mitochondria impairment. Importantly, the GM1‐OS faithfully replicates GM1 activity, emphasizing that even in ALS the protective function of GM1 strictly depends on its pentasaccharide.https://doi.org/10.1002/2211-5463.13727amyotrophic lateral sclerosisexcitotoxicityGM1 gangliosideGM1 oligosaccharideintracellular aggregatesmitochondria
spellingShingle Giulia Lunghi
Erika Di Biase
Emma Veronica Carsana
Alexandre Henriques
Noelle Callizot
Laura Mauri
Maria Grazia Ciampa
Luigi Mari
Nicoletta Loberto
Massimo Aureli
Sandro Sonnino
Michael Spedding
Elena Chiricozzi
Maria Fazzari
GM1 ganglioside exerts protective effects against glutamate‐excitotoxicity via its oligosaccharide in wild‐type and amyotrophic lateral sclerosis motor neurons
FEBS Open Bio
amyotrophic lateral sclerosis
excitotoxicity
GM1 ganglioside
GM1 oligosaccharide
intracellular aggregates
mitochondria
title GM1 ganglioside exerts protective effects against glutamate‐excitotoxicity via its oligosaccharide in wild‐type and amyotrophic lateral sclerosis motor neurons
title_full GM1 ganglioside exerts protective effects against glutamate‐excitotoxicity via its oligosaccharide in wild‐type and amyotrophic lateral sclerosis motor neurons
title_fullStr GM1 ganglioside exerts protective effects against glutamate‐excitotoxicity via its oligosaccharide in wild‐type and amyotrophic lateral sclerosis motor neurons
title_full_unstemmed GM1 ganglioside exerts protective effects against glutamate‐excitotoxicity via its oligosaccharide in wild‐type and amyotrophic lateral sclerosis motor neurons
title_short GM1 ganglioside exerts protective effects against glutamate‐excitotoxicity via its oligosaccharide in wild‐type and amyotrophic lateral sclerosis motor neurons
title_sort gm1 ganglioside exerts protective effects against glutamate excitotoxicity via its oligosaccharide in wild type and amyotrophic lateral sclerosis motor neurons
topic amyotrophic lateral sclerosis
excitotoxicity
GM1 ganglioside
GM1 oligosaccharide
intracellular aggregates
mitochondria
url https://doi.org/10.1002/2211-5463.13727
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