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  • Examination of potential mechanisms of amyloid-induced defects in neuronal transport
    Shah, Sameer B. ...
    Microtubule-based neuronal transport pathways are impaired during the progression of Alzheimer's disease and other neurodegenerative conditions. However, mechanisms leading to defects in transport ... remain to be determined. We quantified morphological changes in neuronal cells following treatment withfibrils and unaggregated peptides of beta-amyloid (Abeta). Abeta fibrils induce axonal and dendritic swellings indicative of impaired transport. In contrast, Abeta peptides induce a necrotic phenotype in both neurons and non-neuronal cells. We tested several popular hypotheses by which aggregated Abeta could disrupt transport. Using fluorescent polystyrene beads, we developed experimental models of physical blockage and localized release of reactive oxygen species (ROS) that reliably induce swellings. Like the beads, Abeta fibrils localize in close proximity to swellings; however, fibril internalization is not required for disrupting transport. ROS and membrane permeability are also unlikely to be responsible for fibril-mediated toxicity. Collectively, our results indicate that multiple initiating factors converge upon pathways of defective transport.
    Source: Neurobiology of disease. - ISSN 0969-9961 (Letn. 36, št. 1, 2009, str. 11-25)
    Type of material - article, component part
    Publish date - 2009
    Language - english
    COBISS.SI-ID - 27161305
    DOI

source: Neurobiology of disease. - ISSN 0969-9961 (Letn. 36, št. 1, 2009, str. 11-25)
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