Laminin affects polymerization, depolymerization and neurotoxicity of Abeta peptide.
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.
Departamento de Biología Celular y Molecular, MIFAB, Facultad de Ciencias Biológicas, Centro de Regulación Celular y Patología, Pontificia Universidad Católica de Chile, Casilla 114-D, Santiago, Chile.
Carlos
C
Morgan
Manuel P
MP
Bugueño
Jorge
J
Garrido
Nibaldo C
NC
Inestrosa
D016229:Amyloid beta-Peptides / Q000633:toxicity* / Q000648:ultrastructure; D000818:Animals; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D006624:Hippocampus / Q000166:cytology; D006801:Humans; D007700:Kinetics; D007797:Laminin / Q000494:pharmacology*; D051379:Mice; D009454:Neurofibrils / Q000648:ultrastructure; D009474:Neurons / Q000166:cytology / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009498:Neurotoxins / Q000037:antagonists & inhibitors; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity* / Q000648:ultrastructure; D011108:Polymers / Q000378:metabolism*; D051381:Rats
D016229:Amyloid beta-Peptides; D007797:Laminin; D018696:Neuroprotective Agents; D009498:Neurotoxins; D010446:Peptide Fragments; D011108:Polymers