Gatti Martina, Zavatti Manuela, Beretti Francesca, Giuliani Daniela, Vandini Eleonora, Ottani Alessandra, Bertucci Emma, Maraldi Tullia
Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena 41125, Italy.
Department of Medical and Surgical Sciences for Mothers, Children and Adults, University of Modena and Reggio Emilia, Azienda Ospedaliero Universitaria Policlinico, Via Del Pozzo 71, 41124 Modena, Italy.
Oxid Med Cell Longev. 2020 Oct 24;2020:2785343. doi: 10.1155/2020/2785343. eCollection 2020.
Alzheimer's disease (AD) is characterized by abnormal protein aggregation, deposition of extracellular -amyloid proteins (A), besides an increase of oxidative stress. Amniotic fluid stem cells (AFSCs) should have a therapeutic potential for neurodegenerative disorders, mainly through a paracrine effect mediated by extracellular vesicles (EV). Here, we examined the effect of EV derived from human AFSCs (AFSC-EV) on the disease phenotypes in an AD neuron primary culture. We observed a positive effect of AFSC-EV on neuron morphology, viability, and A and phospho-Tau levels. This could be due to the apoptotic and autophagic pathway modulation derived from the decrease in oxidative stress. Indeed, reactive oxygen species (ROS) were reduced, while GSH levels were enhanced. This modulation could be ascribed to the presence of ROS regulating enzymes, such as SOD1 present into the AFSC-EV themselves. This study describes the ROS-modulating effects of extracellular vesicles alone, apart from their deriving stem cell, in an AD model, proposing AFSC-EV as a therapeutic tool to stop the progression of AD.
阿尔茨海默病(AD)的特征是蛋白质异常聚集、细胞外β淀粉样蛋白(Aβ)沉积,同时氧化应激增加。羊水干细胞(AFSCs)对神经退行性疾病应具有治疗潜力,主要通过细胞外囊泡(EV)介导的旁分泌作用。在此,我们研究了源自人羊水干细胞的细胞外囊泡(AFSC-EV)对AD神经元原代培养中疾病表型的影响。我们观察到AFSC-EV对神经元形态、活力以及Aβ和磷酸化tau水平有积极作用。这可能是由于氧化应激降低导致凋亡和自噬途径受到调节。事实上,活性氧(ROS)减少,而谷胱甘肽(GSH)水平升高。这种调节可能归因于AFSC-EV自身存在的ROS调节酶,如超氧化物歧化酶1(SOD1)。本研究描述了在AD模型中,细胞外囊泡单独(不考虑其来源干细胞)的ROS调节作用,提出AFSC-EV作为一种治疗工具来阻止AD的进展。