Fazzari, Maria;
Di Biase, Erika;
Zaccagnini, Ludovica;
Henriques, Alexandre;
Callizot, Noëlle;
Ciampa, Maria Grazia;
Mauri, Laura;
... Lunghi, Giulia; + view all
(2023)
GM1 oligosaccharide efficacy against α-synuclein aggregation and toxicity in vitro.
Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids
, 1868
(9)
, Article 159350. 10.1016/j.bbalip.2023.159350.
Preview |
Text
GM1 oligosaccharide efficacy against synuclein.pdf - Accepted Version Download (1MB) | Preview |
Abstract
Fibrillary aggregated α-synuclein represents the neurologic hallmark of Parkinson's disease and is considered to play a causative role in the disease. Although the causes leading to α-synuclein aggregation are not clear, the GM1 ganglioside interaction is recognized to prevent this process. How GM1 exerts these functions is not completely clear, although a primary role of its soluble oligosaccharide (GM1-OS) is emerging. Indeed, we recently identified GM1-OS as the bioactive moiety responsible for GM1 neurotrophic and neuroprotective properties, specifically reverting the parkinsonian phenotype both in in vitro and in vivo models. Here, we report on GM1-OS efficacy against the α-synuclein aggregation and toxicity in vitro. By amyloid seeding aggregation assay and NMR spectroscopy, we demonstrated that GM1-OS was able to prevent both the spontaneous and the prion-like α-synuclein aggregation. Additionally, circular dichroism spectroscopy of recombinant monomeric α-synuclein showed that GM1-OS did not induce any change in α-synuclein secondary structure. Importantly, GM1-OS significantly increased neuronal survival and preserved neurite networks of dopaminergic neurons affected by α-synuclein oligomers, together with a reduction of microglia activation. These data further demonstrate that the ganglioside GM1 acts through its oligosaccharide also in preventing the α-synuclein pathogenic aggregation in Parkinson's disease, opening a perspective window for GM1-OS as drug candidate.
Archive Staff Only
 |
View Item |
