Pro-Inflammatory S100A9 Protein Aggregation Promoted by NCAM1 Peptide Constructs

ACS Chem Biol. 2019 Jul 19;14(7):1410-1417. doi: 10.1021/acschembio.9b00394. Epub 2019 Jun 13.


Amyloid cascade and neuroinflammation are hallmarks of neurodegenerative diseases, and pro-inflammatory S100A9 protein is central to both of them. Here, we have shown that NCAM1 peptide constructs carrying polycationic sequences derived from Aβ peptide (KKLVFF) and PrP protein (KKRPKP) significantly promote the S100A9 amyloid self-assembly in a concentration-dependent manner by making transient interactions with individual S100A9 molecules, perturbing its native structure and acting as catalysts. Since the individual molecule misfolding is a rate-limiting step in S100A9 amyloid aggregation, the effects of the NCAM1 construct on the native S100A9 are so critical for its amyloid self-assembly. S100A9 rapid self-assembly into large aggregated clumps may prevent its amyloid tissue propagation, and by modulating S100A9 aggregation as a part of the amyloid cascade, the whole process may be effectively tuned.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Amyloid / chemistry
  • Amyloid / immunology*
  • Amyloid beta-Peptides / chemistry
  • Amyloid beta-Peptides / immunology
  • CD56 Antigen / chemistry
  • CD56 Antigen / immunology*
  • Calgranulin B / chemistry
  • Calgranulin B / immunology*
  • Humans
  • Inflammation / immunology
  • Models, Molecular
  • Peptide Fragments / chemistry
  • Peptide Fragments / immunology
  • Prions / chemistry
  • Prions / immunology
  • Protein Aggregates
  • Protein Aggregation, Pathological / immunology*


  • Amyloid
  • Amyloid beta-Peptides
  • CD56 Antigen
  • Calgranulin B
  • NCAM1 protein, human
  • Peptide Fragments
  • Prions
  • Protein Aggregates