Browsing by Author "Alarcón, R"

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    Oligodendrocytes damage in Alzheimer's disease
    (2005) Roth, AD; Ramírez, G; Alarcón, R; von Bernhardi, R
    Research on Alzheimer's disease (AD) focuses mainly on neuronal death and synaptic impairment induced by beta-Amyloid peptide (A beta), events at least partially mediated by astrocyte and microglia activation. However, substantial white matter damage and its consequences on brain function warrant the study of oligodendrocytes' compromise in AD and discuss some experimental data indicative of A beta toxicity in culture. We observed that 1 mu M of fibrilogenic A beta peptide damages of astrocytes reduced the A beta-induced damage. This agrees with our previous results showing an astrocyte-mediated protective effect over A beta-induced damage on hippocampal cells and modulation of the activation of microglial cells in culture. Oligodendrocytes protection by astrocytes could be. either by reduction of A beta peptide damages oligodendrocytes in vitro: while pro-inflammatory molecules (1 mu g/ ml LPS + 1 ng/ml IFN gamma) or the presence of astrocytes reduced the A beta-induced damage on hippocampal cells and modulation of the activation of microglial cells in culture. Oligodendrocytes protection by astrocytes could be either by reduction of A beta fibrilogenesis/deposition or prevention of oxidative damage. Likewise, the decrease of A beta-induced damge by proinflammatory molecules could reflect the production of trophic factors by activated oligodendrocytes and/or a metabolic activation as observed during myelination. Considering the association of inflammation with neurodegenerative disease. oligodendrocytes impairement in AD patients could potentiate cell damage under pathological conditions.
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    Stable complexes involving acetylcholinesterase and amyloid-β peptide change the biochemical properties of the enzyme and increase the neurotoxicity of Alzheimer's fibrils
    (1998) Alvarez, A; Alarcón, R; Opazo, C; Campos, EO; Muñoz, FJ; Calderón, FH; Dajas, F; Gentry, MK; Doctor, BP; De Mello, FG; Inestrosa, NC
    Brain acetylcholinesterase (AChE) forms stable complexes with amyloid-beta peptide (A beta) during its assembly into filaments, in agreement with its colocalization with the A beta deposits of Alzheimer's brain. The association of the enzyme with nascent A beta aggregates occurs as early as after 30 min of incubation. Analysis of the catalytic activity of the AChE incorporated into these complexes shows an anomalous behavior reminiscent of the AChE associated with senile plaques, which includes a resistance to low pH, high substrate concentrations, and lower sensitivity to AChE inhibitors. Furthermore, the toxicity of the AChE-amyloid complexes is higher than that of the A beta aggregates alone. Thus, in addition to its possible role as a heterogeneous nucleator during amyloid formation, AChE, by forming such stable complexes, may increase the neurotoxicity of A beta fibrils and thus may determine the selective neuronal loss observed in Alzheimer's brain.