Seeding and Growth of β-Amyloid Aggregates upon Interaction with Neuronal Cell Membranes
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Ruiz-Arias, Álvaro; Paredes Martínez, José Manuel; Di Biase, Chiara; Cuerva Carvajal, Juan Manuel; Girón González, María Dolores; Salto González, Rafael; Gonzalez-Vera, Juan A.; Orte Gutiérrez, ÁngelEditorial
MDPI
Materia
Neurodegenerative diseases Amyloids Misfolding Alzheimer’s disease Fluorescence microscopy FRET
Date
2020-07-16Referencia bibliográfica
Ruiz-Arias, Á., Paredes, J. M., Di Biase, C., Cuerva, J. M., Giron, M. D., Salto, R., ... & Orte, A. (2020). Seeding and Growth of β-Amyloid Aggregates upon Interaction with Neuronal Cell Membranes. International Journal of Molecular Sciences, 21(14), 5035. [doi: 10.3390/ijms21145035]
Sponsorship
Spanish Ministerio de Ciencia, Innovacion y Universidades CTQ2014-56370-R CTQ2017-86568-R CTQ2017-86125-P; Spanish Agencia Estatal de Investigacion; European Union (EU)Abstract
In recent years, the prevalence of amyloid neurodegenerative diseases such as Alzheimer’s
disease (AD) has significantly increased in developed countries due to increased life expectancy.
This amyloid disease is characterized by the presence of accumulations and deposits of β-amyloid
peptide (Aβ) in neuronal tissue, leading to the formation of oligomers, fibers, and plaques. First,
oligomeric intermediates that arise during the aggregation process are currently thought to be
primarily responsible for cytotoxicity in cells. This work aims to provide further insights into
the mechanisms of cytotoxicity by studying the interaction of Aβ aggregates with Neuro-2a (N2a)
neuronal cells and the effects caused by this interaction. For this purpose, we have exploited
the advantages of advanced, multidimensional fluorescence microscopy techniques to determine
whether different types of Aβ are involved in higher rates of cellular toxicity, and we measured the
cellular stress caused by such aggregates by using a fluorogenic intracellular biothiol sensor. Stress
provoked by the peptide is evident by N2a cells generating high levels of biothiols as a defense
mechanism. In our study, we demonstrate that Aβ aggregates act as seeds for aggregate growth upon
interacting with the cellular membrane, which results in cell permeability and damage and induces
lysis. In parallel, these damaged cells undergo a significant increase in intracellular biothiol levels.