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...

Full description

Bibliographic Details
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
Description
Summary: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.
ISSN:2211-5463