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

International Journal of Molecular Sciences

MaríaD. Giron¹  Rafael Salto¹  JuanA. González-Vera²  JoseM. Paredes²  Álvaro Ruiz-Arias²  Chiara Di Biase²  Angel Orte²  JuanM. Cuerva³ 

[1] 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;Departamento de Fisicoquímica, Unidad de Excelencia de Química Aplicada a Biomedicina y Medioambiente, Facultad de Farmacia, Universidad de Granada, Campus Cartuja, 18071 Granada, Spain;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;

关键词: neurodegenerative disease;    amyloid;    misfolding;    Alzheimer’s disease;    fluorescence microscopy;    FRET;   

DOI  :  10.3390/ijms21145035

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown