Pyrroloquinoline quinone influences intracellular alpha-synuclein aggregates

E. Mountford, C. Mathew, R. Ghildyal, Andrea Bugarcic
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Abstract

Abstract Parkinson’s disease (PD) is an irreversible neurodegenerative disorder clinically manifesting in uncontrolled motor symptoms. There are two primary hallmark features of Parkinson’s disease—an irreversible loss of dopaminergic neurons of the substantia nigra pars compacta and formation of intracellular insoluble aggregates called Lewy bodies mostly composed of alpha-synuclein. Using a clinical improvements-first approach, we identified several clinical trials involving consumption of a specific diet or nutritional supplementation that improved motor and nonmotor functions. Here, we aimed to investigate if and how pyrroloquinoline quinone (PQQ) compound disrupts preformed alpha-synuclein deposits using SH-SY5Y cells, widely used Parkinson’s disease cellular model. SH-SY5Y neuroblastoma cells, incubated in presence of potassium chloride (KCl) to induce alpha-synuclein protein aggregation, were treated with PQQ for up to 48 hr. Resulting aggregates were examined and quantified using confocal microscopy. Overall, nutritional compound PQQ reduced the average number and overall size of intracellular cytoplasmic alpha-synuclein aggregates in a PD cellular model.
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吡咯喹啉醌影响细胞内α -突触核蛋白聚集体
摘要帕金森病(PD)是一种不可逆的神经退行性疾病,临床表现为不受控制的运动症状。帕金森氏症有两个主要的标志性特征:一是黑质致密部多巴胺能神经元的不可逆丧失,二是细胞内不溶性聚集体的形成,称为路易体,主要由α -突触核蛋白组成。采用临床改善优先的方法,我们确定了几个涉及特定饮食或营养补充剂的临床试验,这些饮食或营养补充剂可改善运动和非运动功能。在这里,我们旨在研究吡咯喹啉醌(PQQ)化合物是否以及如何在SH-SY5Y细胞中破坏预先形成的α -突触核蛋白沉积,SH-SY5Y细胞是广泛使用的帕金森病细胞模型。SH-SY5Y神经母细胞瘤细胞在氯化钾(KCl)存在下孵育以诱导α -突触核蛋白聚集,PQQ处理长达48小时。使用共聚焦显微镜对所得聚集体进行检测和定量。总的来说,营养化合物PQQ减少了PD细胞模型中胞浆内α -突触核蛋白聚集体的平均数量和总体大小。
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