Synaptotoxicity of Alzheimer beta amyloid can be explained by its membrane perforating property.

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Sepulveda, FJ; Parodi, J; Peoples, RW; Opazo, C; Aguayo, LGDate
2010-07-27Source Title
PLoS OnePublisher
Public Library of Science (PLoS)University of Melbourne Author/s
Opazo Martinez, CarlosAffiliation
Florey Department of Neuroscience and Mental HealthMetadata
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Journal ArticleCitations
Sepulveda, F. J., Parodi, J., Peoples, R. W., Opazo, C. & Aguayo, L. G. (2010). Synaptotoxicity of Alzheimer beta amyloid can be explained by its membrane perforating property.. PLoS One, 5 (7), pp.e11820-. https://doi.org/10.1371/journal.pone.0011820.Access Status
Open AccessOpen Access at PMC
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2910737Abstract
The mechanisms that induce Alzheimer's disease (AD) are largely unknown thereby deterring the development of disease-modifying therapies. One working hypothesis of AD is that Abeta excess disrupts membranes causing pore formation leading to alterations in ionic homeostasis. However, it is largely unknown if this also occurs in native brain neuronal membranes. Here we show that similar to other pore forming toxins, Abeta induces perforation of neuronal membranes causing an increase in membrane conductance, intracellular calcium and ethidium bromide influx. These data reveal that the target of Abeta is not another membrane protein, but that Abeta itself is the cellular target thereby explaining the failure of current therapies to interfere with the course of AD. We propose that this novel effect of Abeta could be useful for the discovery of anti AD drugs capable of blocking these "Abeta perforates". In addition, we demonstrate that peptides that block Abeta neurotoxicity also slow or prevent the membrane-perforating action of Abeta.
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