Browsing by Author "Morgan, C"

Now showing 1 - 4 of 4
  • No Thumbnail Available
    Item
    Acetylcholinesterase-Aβ complexes are more toxic than Aβ fibrils in rat hippocampus -: Effect on rat β-amyloid aggregation, laminin expression, reactive astrocytosis, and neuronal cell loss
    (2004) Reyes, AE; Chacón, MA; Dinamarca, MC; Cerpa, W; Morgan, C; Inestrosa, NC
    Neuropathological changes generated by human amyloid-beta peptide (Abeta) fibrils and Abeta-acetylcholinesterase (Abeta-AChE) complexes were compared in rat hippocampus in vivo. Results showed that Abeta-AChE complexes trigger a more dramatic response in situ than Abeta fibrils alone as characterized by the following features observed 8 weeks after treatment: 1) amyloid deposits were larger than those produced in the absence of AChE. In fact, AChE strongly stimulates rat Abeta aggregation in vitro as shown by turbidity measurements, Congo Red binding, as well as electron microscopy, suggesting that Abeta-AChE deposits observed in vivo probably recruited endogenous Abeta peptide; 2) the appearance of laminin expressing neurons surrounding Abeta-AChE deposits (such deposits are resistant to disaggregation by laminin in vitro); 3) an extensive astrocytosis revealed by both glial fibrillary acidic protein immunoreactivity and number counting of reactive hypertrophic astrocytes; and 4) a stronger neuronal cell loss in comparison with Abeta-injected animals. We conclude that the hippocampal injection of Abeta-AChE complexes results in the appearance of some features reminiscent of Alzheimer-like lesions in rat brain. Our studies are consistent with the notion that Abeta-AChE complexes are more toxic than Abeta fibrils and that AChE triggered some of the neurodegenerative changes observed in Alzheimer's disease brains.
  • No Thumbnail Available
    Item
    Laminin affects polymerization, depolymerization and neurotoxicity of Aβ peptide
    (2002) Morgan, C; Bugueño, MP; Garrido, J; Inestrosa, NC
    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 YFQRYL1 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. (C) 2002 Published by Elsevier Science Inc.
  • No Thumbnail Available
    Item
    Laminin blocks the assembly of wild type Aβ and the Dutch variant peptide into Alzheimer's fibrils
    (1998) Bronfman, FC; Alvarez, A; Morgan, C; Inestrosa, NC
    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 alpha 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 bet important as an inhibitor of A beta amyloidogenesis in vivo, specifically at the level of cerebral blood vessels.
  • No Thumbnail Available
    Item
    Laminin inhibits amyloid-beta-peptide fibrillation
    (1996) Bronfman, FC; Garrido, J; Alvarez, A; Morgan, C; Inestrosa, NC
    Laminin, an important extracellular matrix component is induced by brain injury and colocalizes with amyloid-beta-peptide (A beta) deposits in Alzheimer brains. We report here that laminin inhibits amyloid fibril formation as determined by thioflavin T fluorescence spectroscopy and electron microscopic examination. The inhibition of amyloid formation by laminin was concentration dependent and was observed at a laminin concentration of 300 nM, corresponding to a laminin/A beta protein molar ratio of 1:800. The potential effect of laminin, may prove important to inhibit AP fibrillogenesis in vivo, specifically at the level of cerebral blood vessels.