Laminin blocks the assembly of wild-type A beta and the Dutch variant peptide into Alzheimer's fibrils.
Amyloid fibril formation is believed to be a nucleation-dependent polymerization process which may be influenced by various other factors with important consequences for the development, prevention or treatment of amyloidosis. We have previously shown that laminin inhibits A beta peptide fibril formation in vitro. Here we present a kinetic study that indicates laminin to be a potent anti-amyloidosis factor, as it not only inhibited A beta 1-40 fibril aggregation, but also inhibited the aggregation of the Dutch A beta 1-40 variant, a peptide with a higher capacity to aggregate than the wild-type A beta 1-40. The inhibitory effect of laminin on amyloid fibril formation was not overcome by the addition of pre-formed A beta fibrils, suggesting that laminin inhibits the fibril elongation process. At the present time, however, we cannot rule out the possibility that laminin also affects the initial nucleation process of A beta fibril formation. On other hand, laminin was not able to counteract the amyloid fibril formation promoted by acetylcholinesterase (AChE), another component of the amyloid deposits found in AD brains. The effect of laminin may be important as an inhibitor of A beta amyloidogenesis in vivo, specifically at the level of cerebral blood vessels.
Bronfman
F C
FC
Department of Cellular and Molecular Biology, Catholic University of Chile, Santiago, Chile.
Alvarez
A
A
Morgan
C
C
Inestrosa
N C
NC
D000110:Acetylcholinesterase / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D000686:Amyloidosis / Q000235:genetics / Q000503:physiopathology*; D052160:Benzothiazoles; D005453:Fluorescence; D007700:Kinetics; D007797:Laminin / Q000494:pharmacology*; D009391:Nephelometry and Turbidimetry; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism*; D058225:Plaque, Amyloid / Q000473:pathology; D011485:Protein Binding / Q000502:physiology; D013844:Thiazoles / Q000378:metabolism
D016229:Amyloid beta-Peptides; D052160:Benzothiazoles; D007797:Laminin; D010446:Peptide Fragments; D013844:Thiazoles; C078592:amyloid beta-protein (1-40); C009462:thioflavin T; D000110:Acetylcholinesterase