β-Amyloid Causes Depletion of Synaptic Vesicles Leading to Neurotransmission Failure

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dc.contributor.authorParodi, Jorge
dc.contributor.authorSepulveda, Fernando J.
dc.contributor.authorRoa, Jorge
dc.contributor.authorOpazo, Carlos
dc.contributor.authorInestrosa, Nibaldo C.
dc.contributor.authorAguayo, Luis G.
dc.date.accessioned2025-01-21T00:06:50Z
dc.date.available2025-01-21T00:06:50Z
dc.date.issued2010
dc.description.abstractAlzheimer 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.
dc.fuente.origenWOS
dc.identifier.doi10.1074/jbc.M109.030023
dc.identifier.eissn1083-351X
dc.identifier.urihttps://doi.org/10.1074/jbc.M109.030023
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/95605
dc.identifier.wosidWOS:000273697800029
dc.issue.numero4
dc.language.isoen
dc.pagina.final2514
dc.pagina.inicio2506
dc.revistaJournal of biological chemistry
dc.rightsacceso restringido
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleβ-Amyloid Causes Depletion of Synaptic Vesicles Leading to Neurotransmission Failure
dc.typeartículo
dc.volumen285
sipa.indexWOS
sipa.trazabilidadWOS;2025-01-12
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