Copper(II) and the pathological H50Q α-synuclein mutant: Environment meets genetics

Anna Villar-Piqué, Giulia Rossetti, Salvador Ventura, Paolo Carloni, Claudio O. Fernández, Tiago Fleming Outeiro

Research output: Contribution to journalReview articleResearchpeer-review

11 Citations (Scopus)

Abstract

© 2017 The Author(s). Published with license by Taylor & Francis © 2017, © Anna Villar-Piqué, Giulia Rossetti, Salvador Ventura, Paolo Carloni, Claudio O. Fernández, and Tiago Fleming Outeiro. Copper is one of the metals described to bind the Parkinson disease-related protein α-synuclein (aSyn), and to promote its aggregation. Although histidine at position 50 in the aSyn sequence is one of the most studied copper-anchoring sites, its precise role in copper binding and aSyn aggregation is still unclear. Previous studies suggested that this residue does not significantly affect copper-mediated aSyn aggregation. However, our findings showed that the aggregation of the pathological H50Q aSyn mutant is enhanced by copper hints otherwise. Despite the inexistence of a model for aSyn H50Q-copper complexation, we discuss possible mechanisms by which this metal contributes to the misfolding and self-assembly of this particular aSyn mutant. Considering the genetic association of the H50Q mutation with familial forms of Parkinson disease, and the fact that copper homeostasis is deregulated in this disorder, understanding the interplay between both factors will shed light into the molecular and cellular mechanisms triggering the development and spreading of the aSyn pathology.
Original languageEnglish
Article numbere1270484
JournalCommunicative and Integrative Biology
Volume10
Issue number1
DOIs
Publication statusPublished - 2 Jan 2017

Keywords

  • amyloid
  • copper
  • H50Q mutation
  • Parkinson disease
  • protein aggregation
  • α-synuclein

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