Dopamine promotes α-synuclein aggregation into SDS-resistant soluble oligomers via a distinct folding pathway Academic Article uri icon

abstract

  • Dopamine (DA) and alpha-synuclein (alpha-SN) are two key molecules associated with Parkinson's disease (PD). We have identified a novel action of DA in the initial phase of alpha-SN aggregation and demonstrate that DA induces alpha-SN to form soluble, SDS-resistant oligomers. The DA:alpha-SN oligomeric species are not amyloidogenic as they do not react with thioflavin T and lack the typical amyloid fibril structures as visualized with electron microscopy. Circular dichroism studies indicate that in the presence of lipid membranes DA interacts with alpha-SN, causing an alteration to the structure of the protein. Furthermore, DA inhibited the formation of iron-induced alpha-SN amyloidogenic aggregates, suggesting that DA acts as a dominant modulator of alpha-SN aggregation. These observations support the paradigm emerging for other neurodegenerative diseases that the toxic species is represented by a soluble oligomer and not the insoluble fibril.

authors

  • Cappai, Roberto
  • Leck, Su-Ling
  • Tew, Deborah J
  • Williamson, Nicholas A
  • Smith, David P
  • Galatis, Denise
  • Sharples, Robyn A
  • Curtain, Cyril C
  • Ali, Feda’ E
  • Cherny, Robert A
  • Culvenor, Janetta G
  • Bottomley, Stephen P
  • Masters, Colin L
  • Barnham, Kevin J
  • Hill, Andrew F

publication date

  • August 2005