Oxidative stress induces amyloid-like aggregate formation of NACP/alpha-synuclein in vitro

Neuroreport. 1999 Mar 17;10(4):717-21. doi: 10.1097/00001756-199903170-00011.


The precursor of non-amyloid beta protein component of Alzheimer's disease amyloid (NACP/alpha-synuclein), found in Lewy bodies of Parkinson's disease (PD), is a presynaptic protein genetically linked to some familial types PD. Mechanisms of abnormal NACP/alpha-synuclein aggregation in neurodegenerative diseases are unclear. Since oxidative stress might play a role in PD pathogenesis, we investigated the role of iron and peroxide in NACP/alpha-synuclein aggregation. Immunoblot analysis showed that human NACP/alpha-synuclein (but not beta-synuclein) aggregated in the presence of ferric ion and was inhibited by the iron chelator deferoxamine. Ferrous ion was not effective by itself, but it potentially aggregated NACP/alpha-synuclein in the presence of hydrogen peroxide. NACP/ alpha-synuclein aggregates displayed strong thioflavine-S and congo-red reactivity, reminiscent of amyloid. This study suggests that NACP/alpha-synuclein aggregation might be closely related to oxidative reactions which may play a critical role in neurodegeneration in disorders with Lewy bodies.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alzheimer Disease / metabolism
  • Amyloid / chemistry*
  • Amyloid / drug effects
  • Amyloid / ultrastructure
  • Catalysis
  • Chlorides
  • Ferric Compounds / chemistry
  • Ferrous Compounds / chemistry
  • Humans
  • Nerve Tissue Proteins / chemistry*
  • Nerve Tissue Proteins / drug effects
  • Nerve Tissue Proteins / ultrastructure
  • Oxidation-Reduction
  • Oxidative Stress / physiology*
  • Recombinant Proteins / chemistry
  • Synucleins
  • alpha-Synuclein
  • beta-Synuclein


  • Amyloid
  • Chlorides
  • Ferric Compounds
  • Ferrous Compounds
  • Nerve Tissue Proteins
  • Recombinant Proteins
  • SNCA protein, human
  • SNCB protein, human
  • Synucleins
  • alpha-Synuclein
  • beta-Synuclein
  • ferrous chloride
  • ferric chloride