S100A9 Alters the Pathway of Alpha-Synuclein Amyloid Aggregation

Int J Mol Sci. 2021 Jul 26;22(15):7972. doi: 10.3390/ijms22157972.

Abstract

The formation of amyloid fibril plaques in the brain creates inflammation and neuron death. This process is observed in neurodegenerative disorders, such as Alzheimer's and Parkinson's diseases. Alpha-synuclein is the main protein found in neuronal inclusions of patients who have suffered from Parkinson's disease. S100A9 is a calcium-binding, pro-inflammation protein, which is also found in such amyloid plaques. To understand the influence of S100A9 on the aggregation of α-synuclein, we analyzed their co-aggregation kinetics and the resulting amyloid fibril structure by Fourier-transform infrared spectroscopy and atomic force microscopy. We found that the presence of S100A9 alters the aggregation kinetics of α-synuclein and stabilizes the formation of a particular amyloid fibril structure. We also show that the solution's ionic strength influences the interplay between S100A9 and α-synuclein, stabilizing a different structure of α-synuclein fibrils.

Keywords: AFM; FTIR; S100A9; amyloid proteins; fibrils; synuclein.

MeSH terms

  • Amyloid / chemistry*
  • Calgranulin B / chemistry*
  • Humans
  • Protein Aggregates*
  • Recombinant Proteins / chemistry
  • alpha-Synuclein / chemistry*

Substances

  • Amyloid
  • Calgranulin B
  • Protein Aggregates
  • Recombinant Proteins
  • S100A9 protein, human
  • SNCA protein, human
  • alpha-Synuclein