Past evidence has shown that the exogenous administration of GM1 ganglioside slowed neuronal death in preclinical models of Parkinson's disease, a neurodegenerative disorder characterized by the progressive loss of dopamine-producing neurons: however, the physical and chemical properties of GM1 (i.e., amphiphilicity) limited its clinical application, as the crossing of the blood-brain barrier is denied. Recently, we demonstrated that the GM1 oligosaccharide head group (GM1-OS) is the GM1 bioactive portion that, interacting with the TrkA-NGF complex at the membrane surface, promotes the activation of a multivariate network of intracellular events regulating neuronal differentiation, protection, and reparation. Here, we evaluated the GM1-OS neuroprotective potential against the Parkinson's disease-linked neurotoxin MPTP, which destroys dopaminergic neurons by affecting mitochondrial bioenergetics and causing ROS overproduction. In dopaminergic and glutamatergic primary cultures, GM1-OS administration significantly increased neuronal survival, preserved neurite network, and reduced mitochondrial ROS production enhancing the mTOR/Akt/GSK3 beta pathway. These data highlight the neuroprotective efficacy of GM1-OS in parkinsonian models through the implementation of mitochondrial function and reduction in oxidative stress.
GM1 Oligosaccharide Efficacy in Parkinson’s Disease: Protection against MPTP / M. Fazzari, G. Lunghi, A. Henriques, N. Callizot, M.G. Ciampa, L. Mauri, S. Prioni, E.V. Carsana, N. Loberto, M. Aureli, L. Mari, S. Sonnino, E. Chiricozzi, E. DI BIASE. - In: BIOMEDICINES. - ISSN 2227-9059. - 11:5(2023 Apr), pp. 1305.1-1305.14. [10.3390/biomedicines11051305]
GM1 Oligosaccharide Efficacy in Parkinson’s Disease: Protection against MPTP
M. FazzariCo-primo
;G. LunghiCo-primo
;M.G. Ciampa;L. Mauri;S. Prioni;E.V. Carsana;N. Loberto;M. Aureli;S. Sonnino;E. Chiricozzi
Penultimo
;E. DI BIASE
Ultimo
2023
Abstract
Past evidence has shown that the exogenous administration of GM1 ganglioside slowed neuronal death in preclinical models of Parkinson's disease, a neurodegenerative disorder characterized by the progressive loss of dopamine-producing neurons: however, the physical and chemical properties of GM1 (i.e., amphiphilicity) limited its clinical application, as the crossing of the blood-brain barrier is denied. Recently, we demonstrated that the GM1 oligosaccharide head group (GM1-OS) is the GM1 bioactive portion that, interacting with the TrkA-NGF complex at the membrane surface, promotes the activation of a multivariate network of intracellular events regulating neuronal differentiation, protection, and reparation. Here, we evaluated the GM1-OS neuroprotective potential against the Parkinson's disease-linked neurotoxin MPTP, which destroys dopaminergic neurons by affecting mitochondrial bioenergetics and causing ROS overproduction. In dopaminergic and glutamatergic primary cultures, GM1-OS administration significantly increased neuronal survival, preserved neurite network, and reduced mitochondrial ROS production enhancing the mTOR/Akt/GSK3 beta pathway. These data highlight the neuroprotective efficacy of GM1-OS in parkinsonian models through the implementation of mitochondrial function and reduction in oxidative stress.File | Dimensione | Formato | |
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