Laminin affects polymerization, depolymerization and neurotoxicity of Abeta peptide

Peptides. 2002 Jul;23(7):1229-40. doi: 10.1016/s0196-9781(02)00058-x.

Abstract

Amyloid deposition in Alzheimer fibrils forms neurotoxic senile plaques in a process that may be modulated by associated proteins. In this work we demonstrate the ability of laminin-1 and laminin-2 to inhibit fibril formation and toxicity on cultured rat hippocampal neurons. We confirm that the laminin-1-derived peptide YFQRYLI inhibits efficiently both fibril formation and neurotoxicity and show that the IKVAV peptide inhibits amyloid neurotoxicity despite its slight inhibition of fibril formation. On other hand, laminin-1 induces disaggregation of preformed fibrils in vitro, characterized as a progressive disassembly of fibrils into protofibrils and further clearance of these latter species, leading to a continual inhibition of amyloid neurotoxicity.

Publication types

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

MeSH terms

  • Amyloid beta-Peptides / toxicity*
  • Amyloid beta-Peptides / ultrastructure
  • Animals
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Hippocampus / cytology
  • Humans
  • Kinetics
  • Laminin / pharmacology*
  • Mice
  • Neurofibrils / ultrastructure
  • Neurons / cytology
  • Neurons / drug effects*
  • Neuroprotective Agents / pharmacology*
  • Neurotoxins / antagonists & inhibitors
  • Peptide Fragments / chemistry
  • Peptide Fragments / pharmacology*
  • Peptide Fragments / toxicity*
  • Peptide Fragments / ultrastructure
  • Polymers / metabolism*
  • Rats

Substances

  • Amyloid beta-Peptides
  • Laminin
  • Neuroprotective Agents
  • Neurotoxins
  • Peptide Fragments
  • Polymers