The Cytotoxic Effect of α-Synuclein Aggregates

Francisco Melo, Leonardo Caballero, Esteban Zamorano, Natalia Ventura, Camilo Navarro, Irving Doll, Pedro Zamorano, Alberto Cornejo

Resultado de la investigación: Contribución a una revistaArtículorevisión exhaustiva

Resumen

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.

Idioma originalInglés
Páginas (desde-hasta)526-532
Número de páginas7
PublicaciónChemPhysChem
Volumen22
N.º6
DOI
EstadoPublicada - 17 mar 2021

Áreas temáticas de ASJC Scopus

  • Óptica y física atómica y molecular
  • Química física y teórica

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