Laminin 1 attenuates beta-amyloid peptide Abeta(1-40) neurotoxicity of cultured fetal rat cortical neurons.
A growing amount of evidence indicates the involvement of extracellular matrix components, especially laminins, in the development of Alzheimer's disease, although their role remains unclear. In this study, we clearly demonstrate that laminin 1 inhibits beta-amyloid peptide (Abeta)-induced neuronal cell death by preventing the fibril formation and interaction of the Abeta peptide with cell membranes. The presence of laminin at a laminin/Abeta peptide molar ratio of 1:800 significantly inhibits the Abeta-induced apoptotic events, together with inhibition of amyloid fibril formation. The inhibitory effects of laminin 1 were time- and dose-dependent, whereas laminin 2 had less effect on Abeta neurotoxicity. A preincubation of laminin and Abeta was not required to observe the protective effect of laminin, suggesting a direct interaction between laminin 1 and Abeta. Moreover, laminin had no effect on the toxicity of the fibrillar Abeta peptide, suggesting an interaction of laminin with nonfibrillar species of the Abeta peptide, sequestering the peptide in a soluble form. These data extend our understanding of laminin-dependent binding of Abeta and highlight the possible modulation role of laminin regarding Abeta aggregation and neurotoxicity in vivo.
Drouet
B
B
INSERM U-505, Institut des Cordelliers, Paris, France.
Pinçon-Raymond
M
M
Chambaz
J
J
Pillot
T
T
D000544:Alzheimer Disease / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D005333:Fetus / Q000166:cytology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D007797:Laminin / Q000494:pharmacology*; D009410:Nerve Degeneration / Q000188:drug therapy / Q000378:metabolism; D016874:Neurofibrillary Tangles / Q000378:metabolism; D009474:Neurons / Q000166:cytology* / Q000187:drug effects* / Q000201:enzymology; D018696:Neuroprotective Agents / Q000494:pharmacology; D010446:Peptide Fragments / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D012995:Solubility
D016229:Amyloid beta-Peptides; D007797:Laminin; D018696:Neuroprotective Agents; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); D007770:L-Lactate Dehydrogenase