Institution: | 1. Departamento de Física, Universidad de Santiago de Chile, Avenida Ecuador 3493, Santiago, Chile
Center for Soft Matter Research, SMAT-C, Universidad de Santiago de Chile, Avenida Bernardo O'Higgins 3363, Santiago, Chile;2. Escuela de Tecnología Médica, Universidad Andrés Bello, Echaurren 183, Laboratorio Catem V, Santiago, Chile;3. Departamento Biomédico, Instituto Antofagasta, Universidad de Antofagasta, Universidad de Antofagasta, Antofagasta, Chile, Antofagasta, Chile |
Abstract: | Parkinson's disease is a neurodegenerative disorder involving a functional protein, α-synuclein, whose primary function is related to vesicle trafficking. However, α-synuclein is prone to form aggregates, and these inclusions, known as Lewy bodies, are the hallmark of Parkinson's disease. α-synuclein can alter its conformation and acquire aggregating capacity, forming aggregates containing β-sheets. This protein's pathogenic importance is based on its ability to form oligomers that impair synaptic transmission and neuronal function by increasing membrane permeability and altering homeostasis, generating a deleterious effect over cells. First, we establish that oligomers interfere with the mechanical properties of 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) membrane, as demonstrated by nanoindentation curves. In contrast, nanoindentation revealed that the α-synuclein monomer's presence leads to a much more resistant lipid bilayer. Moreover, the oligomers’ interaction with cell membranes can promote lactate dehydrogenase (LDH) release, suggesting the activation of cytotoxic events. |