Alpha-Synuclein (AS) is the protein playing the major role in Parkinson's disease (PD), a neurological disorder characterized by the degeneration of dopaminergic neurons and the accumulation of AS into amyloid plaques. The aggregation of AS into intermediate aggregates, called oligomers, and their pathological relation with biological membranes are considered key steps in the development and progression of the disease. Here we propose a multi-technique approach to study the effects of AS in its monomeric and oligomeric forms on artificial lipid membranes containing GM1 ganglioside. GM1 is a component of functional membrane micro-domains, called lipid rafts, and has been demonstrated to bind AS in neurons. With the aim to understand the relation between gangliosides and AS, here we exploit the complementarity of microscopy (Atomic Force Microscopy) and neutron scattering (Small Angle Neutron Scattering and Neutron Reflectometry) techniques to analyze the structural changes of two different membranes (Phosphatidylcholine and Phosphatidylcholine/GM1) upon binding with AS. We observe the monomer- and oligomer-interactions are both limited to the external membrane leaflet and that the presence of ganglioside leads to a stronger interaction of the membranes and AS in its monomeric and oligomeric forms with a stronger aggressiveness in the latter. These results support the hypothesis of the critical role of lipid rafts not only in the biofunctioning of the protein, but even in the development and the progression of the Parkinson's disease.
GM1 Ganglioside role in the interaction of Alpha-synuclein with lipid membranes: Morphology and structure / F. Perissinotto, V. Rondelli, P. Parisse, N. Tormena, A. Zunino, L. Almasy, D.G. Merkel, L. Bottyan, S. Sajti, L. Casalis. - In: BIOPHYSICAL CHEMISTRY. - ISSN 0301-4622. - 255(2019 Dec).
|Titolo:||GM1 Ganglioside role in the interaction of Alpha-synuclein with lipid membranes: Morphology and structure|
RONDELLI, VALERIA MARIA (Corresponding)
|Parole Chiave:||AFM; Alphasynuclein; GM1; Model membrane; Neutron reflectometry; Neutron scattering; Dimyristoylphosphatidylcholine; G(M1) Ganglioside; Humans; Lipid Bilayers; Microscopy, Atomic Force; Neutron Diffraction; Phosphatidylcholines; Protein Aggregates; Protein Binding; Scattering, Small Angle; alpha-Synuclein|
|Settore Scientifico Disciplinare:||Settore FIS/07 - Fisica Applicata(Beni Culturali, Ambientali, Biol.e Medicin)|
|Data di pubblicazione:||dic-2019|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1016/j.bpc.2019.106272|
|Appare nelle tipologie:||01 - Articolo su periodico|