α-Synuclein Over-Expression Induces Increased Iron Accumulation and Redistribution in Iron-Exposed Neurons

Richard Ortega, Asuncion Carmona, Stéphane Roudeau, Laura Perrin, Tanja Dučić, Eleonora Carboni, Sylvain Bohic, Peter Cloetens, Paul Lingor

Research output: Contribution to journalArticlepeer-review

61 Scopus citations

Abstract

Parkinson’s disease is the most common α-synucleinopathy, and increased levels of iron are found in the substantia nigra of Parkinson’s disease patients, but the potential interlink between both molecular changes has not been fully understood. Metal to protein binding assays have shown that α-synuclein can bind iron in vitro; therefore, we hypothesized that iron content and iron distribution could be modified in cellulo, in cells over-expressing α-synuclein. Owing to particle-induced X-ray emission and synchrotron X-ray fluorescence chemical nano-imaging, we were able to quantify and describe the iron distribution at the subcellular level. We show that, in neurons exposed to excess iron, the mere over-expression of human α-synuclein results in increased levels of intracellular iron and in iron redistribution from the cytoplasm to the perinuclear region within α-synuclein-rich inclusions. Reproducible results were obtained in two distinct recombinant expression systems, in primary rat midbrain neurons and in a rat neuroblastic cell line (PC12), both infected with viral vectors expressing human α-synuclein. Our results link two characteristic molecular features found in Parkinson’s disease, the accumulation of α-synuclein and the increased levels of iron in the substantia nigra.

Original languageEnglish
Pages (from-to)1925-1934
Number of pages10
JournalMolecular Neurobiology
Volume53
Issue number3
DOIs
StatePublished - 1 Apr 2016
Externally publishedYes

Keywords

  • Iron
  • Neuroimaging
  • Parkinson’s disease
  • Synchrotron
  • α-Synuclein

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