The Cytotoxic Effect of α-Synuclein Aggregates

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

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)526-532
Number of pages7
JournalChemPhysChem
Volume22
Issue number6
DOIs
Publication statusPublished - 17 Mar 2021

Keywords

  • aggregates
  • membrane
  • nanoindentation
  • Parkinson's disease
  • toxicity

ASJC Scopus subject areas

  • Atomic and Molecular Physics, and Optics
  • Physical and Theoretical Chemistry

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