Data di Pubblicazione:
2023
Citazione:
GM1 oligosaccharide efficacy against α-synuclein aggregation and toxicity in vitro / M. Fazzari, E. Di Biase, L. Zaccagnini, A. Henriques, N. Callizot, M.G. Ciampa, L. Mauri, E.V. Carsana, N. Loberto, M. Aureli, L. Mari, M. Civera, F. Vasile, S. Sonnino, T. Bartels, E. Chiricozzi, G. Lunghi. - In: BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS. - ISSN 1388-1981. - 1868:9(2023 Sep), pp. 159350.1-159350.9. [10.1016/j.bbalip.2023.159350]
Abstract:
Fibrillary aggregated a-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 a-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 a-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 a-synuclein aggregation. Additionally, circular dichroism spectroscopy of recombinant monomeric a-synuclein showed that GM1-OS did not induce any change in a-synuclein secondary structure. Importantly, GM1-OS significantly increased neuronal survival and preserved neurite networks of dopaminergic neurons affected by a-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 a-synuclein pathogenic aggregation in Parkinson's disease, opening a perspective window for GM1-OS as drug candidate.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
GM1 ganglioside; GM1 oligosaccharide; Parkinson's disease; Plasma membrane signaling; α-Synuclein;
Elenco autori:
M. Fazzari, E. Di Biase, L. Zaccagnini, A. Henriques, N. Callizot, M.G. Ciampa, L. Mauri, E.V. Carsana, N. Loberto, M. Aureli, L. Mari, M. Civera, F. Vasile, S. Sonnino, T. Bartels, E. Chiricozzi, G. Lunghi
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