Browsing by Author "Opazo, Carlos"

Now showing 1 - 3 of 3
  • No Thumbnail Available
    Item
    Intracellular amyloid formation in muscle cells of Aβ-transgenic Caenorhabditis elegans: determinants and physiological role in copper detoxification
    (2009) Minniti, Alicia N.; Rebolledo, Daniela L.; Grez, Paula M.; Fadic, Ricardo; Aldunate, Rebeca; Volitakis, Irene; Cherny, Robert A.; Opazo, Carlos; Masters, Colin; Bush, Ashley I.; Inestrosa, Nibaldo C.
    Background: The amyloid beta-peptide is a ubiquitous peptide, which is prone to aggregate forming soluble toxic oligomers and insoluble less-toxic aggregates. The intrinsic and external/environmental factors that determine A beta aggregation in vivo are poorly understood, as well as the cellular meaning of this process itself. Genetic data as well as cell biological and biochemical evidence strongly support the hypothesis that A beta is a major player in the onset and development of Alzheimer's disease. In addition, it is also known that A beta is involved in Inclusion Body Myositis, a common myopathy of the elderly in which the peptide accumulates intracellularly.
  • Thumbnail Image
    Item
  • No Thumbnail Available
    Item
    β-Amyloid Causes Depletion of Synaptic Vesicles Leading to Neurotransmission Failure
    (2010) Parodi, Jorge; Sepulveda, Fernando J.; Roa, Jorge; Opazo, Carlos; Inestrosa, Nibaldo C.; Aguayo, Luis G.
    Alzheimer disease is a progressive neurodegenerative brain disorder that leads to major debilitating cognitive deficits. It is believed that the alterations capable of causing brain circuitry dysfunctions have a slow onset and that the full blown disease may take several years to develop. Therefore, it is important to understand the early, asymptomatic, and possible reversible states of the disease with the aim of proposing preventive and disease-modifying therapeutic strategies. It is largely unknown how amyloid beta-peptide (A beta), a principal agent in Alzheimer disease, affects synapses in brain neurons. In this study, we found that similar to other pore-forming neurotoxins, A beta induced a rapid increase in intracellular calcium and miniature currents, indicating an enhancement in vesicular transmitter release. Significantly, blockade of these effects by low extracellular calcium and a peptide known to act as an inhibitor of the A beta-induced pore prevented the delayed failure, indicating that A beta blocks neurotransmission by causing vesicular depletion. This new mechanism for A beta synaptic toxicity should provide an alternative pathway to search for small molecules that can antagonize these effects of A beta.