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Article

Seeding and Growth of β-Amyloid Aggregates upon Interaction with Neuronal Cell Membranes

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Departamento de Fisicoquímica, Unidad de Excelencia de Química Aplicada a Biomedicina y Medioambiente, Facultad de Farmacia, Universidad de Granada, Campus Cartuja, 18071 Granada, Spain
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Department of Biomolecular Sciences, University of Urbino Carlo Bo, 61029 Urbino, Italy
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Departamento de Química Orgánica, Unidad de Excelencia de Química Aplicada a Biomedicina y Medioambiente, Facultad de Ciencias, Universidad de Granada, Campus Fuentenueva, 18071 Granada, Spain
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Departamento de Bioquímica y Biología Molecular II, Unidad de Excelencia de Química Aplicada a Biomedicina y Medioambiente, Facultad de Farmacia, Universidad de Granada, Campus Cartuja, 18071 Granada, Spain
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Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(14), 5035; https://doi.org/10.3390/ijms21145035
Received: 28 June 2020 / Revised: 14 July 2020 / Accepted: 15 July 2020 / Published: 16 July 2020
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. View Full-Text
Keywords: neurodegenerative disease; amyloid; misfolding; Alzheimer’s disease; fluorescence microscopy; FRET neurodegenerative disease; amyloid; misfolding; Alzheimer’s disease; fluorescence microscopy; FRET
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MDPI and ACS Style

Ruiz-Arias, Á.; Paredes, J.M.; Di Biase, C.; Cuerva, J.M.; Giron, M.D.; Salto, R.; González-Vera, J.A.; Orte, A. Seeding and Growth of β-Amyloid Aggregates upon Interaction with Neuronal Cell Membranes. Int. J. Mol. Sci. 2020, 21, 5035. https://doi.org/10.3390/ijms21145035

AMA Style

Ruiz-Arias Á, Paredes JM, Di Biase C, Cuerva JM, Giron MD, Salto R, González-Vera JA, Orte A. Seeding and Growth of β-Amyloid Aggregates upon Interaction with Neuronal Cell Membranes. International Journal of Molecular Sciences. 2020; 21(14):5035. https://doi.org/10.3390/ijms21145035

Chicago/Turabian Style

Ruiz-Arias, Álvaro, Jose M. Paredes, Chiara Di Biase, Juan M. Cuerva, María D. Giron, Rafael Salto, Juan A. González-Vera, and Angel Orte. 2020. "Seeding and Growth of β-Amyloid Aggregates upon Interaction with Neuronal Cell Membranes" International Journal of Molecular Sciences 21, no. 14: 5035. https://doi.org/10.3390/ijms21145035

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