The crucial role of ganglioside GM1 in the regulation of neural homeostasis has been assessed by several studies. Recently we shed new light on the molecular basis underlying GM1 effects demonstrating that GM1 oligosaccharide directly binds TrkA receptor and triggers MAPK pathway activation leading to neuronal differentiation and protection. Following its exogenous administration, proteomic analysis revealed an increased expression of proteins involved in several biochemical mechanisms, including mitochondrial bioenergetics. Based on these data, we investigated the possible effect of GM1 oligosaccharide administration on mitochondrial function. We show that wild-type Neuro2a cells exposed to GM1 oligosaccharide displayed an increased mitochondrial density and an enhanced mitochondrial activity together with reduced reactive oxygen species levels. Interestingly, using a Neuro2a model of mitochondrial dysfunction, we found an increased mitochondrial oxygen consumption rate as well as increased complex I and II activities upon GM1 oligosaccharide administration. Taken together, our data identify GM1 oligosaccharide as a mitochondrial regulator that by acting at the plasma membrane level triggers biochemical signaling pathway inducing mitochondriogenesis and increasing mitochondrial activity. Although further studies are necessary, the capability to enhance the function of impaired mitochondria points to the therapeutic potential of the GM1 oligosaccharide for the treatment of pathologies where these organelles are compromised, including Parkinson's disease.

The oligosaccharide portion of ganglioside GM1 regulates mitochondrial function in neuroblastoma cells / M. Fazzari, M. Audano, G. Lunghi, E. Di Biase, N. Loberto, L. Mauri, N. Mitro, S. Sonnino, E. Chiricozzi. - In: GLYCOCONJUGATE JOURNAL. - ISSN 0282-0080. - 37:3(2020 Jun), pp. 293-306. [10.1007/s10719-020-09920-4]

The oligosaccharide portion of ganglioside GM1 regulates mitochondrial function in neuroblastoma cells

M. Fazzari;M. Audano;G. Lunghi;E. Di Biase;N. Loberto;L. Mauri;N. Mitro
;
S. Sonnino;E. Chiricozzi
2020

Abstract

The crucial role of ganglioside GM1 in the regulation of neural homeostasis has been assessed by several studies. Recently we shed new light on the molecular basis underlying GM1 effects demonstrating that GM1 oligosaccharide directly binds TrkA receptor and triggers MAPK pathway activation leading to neuronal differentiation and protection. Following its exogenous administration, proteomic analysis revealed an increased expression of proteins involved in several biochemical mechanisms, including mitochondrial bioenergetics. Based on these data, we investigated the possible effect of GM1 oligosaccharide administration on mitochondrial function. We show that wild-type Neuro2a cells exposed to GM1 oligosaccharide displayed an increased mitochondrial density and an enhanced mitochondrial activity together with reduced reactive oxygen species levels. Interestingly, using a Neuro2a model of mitochondrial dysfunction, we found an increased mitochondrial oxygen consumption rate as well as increased complex I and II activities upon GM1 oligosaccharide administration. Taken together, our data identify GM1 oligosaccharide as a mitochondrial regulator that by acting at the plasma membrane level triggers biochemical signaling pathway inducing mitochondriogenesis and increasing mitochondrial activity. Although further studies are necessary, the capability to enhance the function of impaired mitochondria points to the therapeutic potential of the GM1 oligosaccharide for the treatment of pathologies where these organelles are compromised, including Parkinson's disease.
GM1 ganglioside; GM1 oligosaccharide; Mitochondria dysfunctions; Mitochondrial biogenesis; Mitochondrial function; Plasma membrane signaling
Settore BIO/10 - Biochimica
   Dipartimenti di Eccellenza 2018-2022 - Dipartimento di FILOSOFIA
   MINISTERO DELL'ISTRUZIONE E DEL MERITO
giu-2020
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/730258
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