The newly discovered Parkinson's disease associated Finnish mutation (A53E) attenuates α-synuclein aggregation and membrane binding

Biochemistry. 2014 Oct 21;53(41):6419-21. doi: 10.1021/bi5010365. Epub 2014 Oct 10.

Abstract

α-Synuclein (α-Syn) oligomerization and amyloid formation are associated with Parkinson's disease (PD) pathogenesis. Studying familial α-Syn mutants associated with early onset PD has therapeutic importance. Here we report the aggregation kinetics and other biophysical properties of a newly discovered PD associated Finnish mutation (A53E). Our in vitro study demonstrated that A53E attenuated α-Syn aggregation and amyloid formation without altering the major secondary structure and initial oligomerization tendency. Further, A53E showed reduced membrane binding affinity compared to A53T and WT. The present study would help to delineate the role of A53E mutation in early onset PD pathogenesis.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Substitution
  • Amyloid / chemistry
  • Amyloid / genetics*
  • Amyloid / metabolism
  • Circular Dichroism
  • Finland
  • Fluorescent Dyes / chemistry
  • Humans
  • Kinetics
  • Lipid Bilayers
  • Microscopy, Atomic Force
  • Mutation*
  • Parkinson Disease / genetics*
  • Parkinson Disease / metabolism
  • Phosphatidylcholines / metabolism
  • Phosphatidylethanolamines / metabolism
  • Protein Aggregation, Pathological
  • Protein Structure, Secondary
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / metabolism
  • Spectrometry, Fluorescence
  • Surface Plasmon Resonance
  • Surface Properties
  • alpha-Synuclein / chemistry
  • alpha-Synuclein / genetics*
  • alpha-Synuclein / metabolism

Substances

  • Amyloid
  • Fluorescent Dyes
  • Lipid Bilayers
  • Phosphatidylcholines
  • Phosphatidylethanolamines
  • Recombinant Proteins
  • SNCA protein, human
  • alpha-Synuclein

Supplementary concepts

  • Parkinson Disease, Familial, Type 1