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Formation of amyloid fibers triggered by phosphatidylserine-containing membranes

Hongxia Zhao1, Esa K J Tuominen, Paavo K J Kinnunen

  • 1Helsinki Biophysics and Biomembrane Group, Institute of Biomedicine, P.O. Box 63 (Haartmaninkatu 8), University of Helsinki, FIN-00014 Helsinki, Finland.

Biochemistry
|August 11, 2004
PubMed

Insights

Acidic phospholipids, like phosphatidylserine (PS), trigger rapid amyloid fibril formation in various proteins. This discovery links amyloidogenesis, protein cytotoxicity, and membrane function, offering insights into neurodegenerative diseases.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Background:

  • Protein misfolding and amyloid fibril deposition cause devastating diseases like Alzheimer's and Parkinson's.
  • Mechanisms initiating in vivo amyloid formation remain largely unknown, as mutations are infrequent triggers.

Purpose of the Study:

  • To investigate the role of cellular membranes and phospholipids in initiating protein misfolding and amyloid fibril formation.
  • To explore the connection between amyloid formation, protein cytotoxicity, and membrane perturbation.

Main Methods:

  • Incubation of various proteins (lysozyme, insulin, etc.) with membranes containing phosphatidylserine (PS).
  • Congo red staining to identify amyloid characteristics (birefringence).
  • Fluorescent lipid tracers to confirm phospholipid incorporation into fibers.

Main Results:

  • Phosphatidylserine (PS)-containing membranes rapidly induced fiber formation in multiple proteins.
  • Induced fibers exhibited characteristic amyloid light green birefringence with Congo red staining.
  • Acidic phospholipids may create a physiological low-pH environment, promoting in vivo fibril formation.

Conclusions:

  • Acidic phospholipids, particularly PS, are potent inducers of amyloid fibril formation.
  • PS-protein interactions may mediate the cytotoxicity of aggregated fibrils by perturbing membrane functions.
  • This finding provides a unified perspective on amyloidogenesis triggers, cytotoxicity, and membrane interactions.

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