Parkinson’s disease (PD) is a progressive neurological disorder associated with the loss of dopaminergic neurons (DNs) in the substantia nigra and the widespread accumulation of α-synuclein (α-syn) protein, leading to motor impairments and eventual cognitive dysfunction. In-vitro cell cultures and in-vivo animal models have provided the opportunity to investigate the PD pathological hallmarks and identify different therapeutic compounds. However, PD pathogenesis and causes are still not well understood, and effective inhibitory drugs for PD are yet to be discovered. Biologically simple but pathologically relevant disease models and advanced screening technologies are needed to reveal the mechanisms underpinning protein aggregation and PD progression. For instance, Caenorhabditis elegans (C. elegans) offers many advantages for fundamental PD neurobehavioral studies including a simple, well-mapped, and accessible neuronal system, genetic homology to humans, body transparency and amenability to genetic manipulation. Several transgenic worm strains that exhibit multiple PD-related phenotypes have been developed to perform neuronal and behavioral assays and drug screening. However, in conventional worm-based assays, the commonly used techniques are equipment-intensive, slow and low in throughput. Over the past two decades, microfluidics technology has contributed significantly to automation and control of C. elegans assays. In this review, we focus on C. elegans PD models and the recent advancements in microfluidic platforms used for manipulation, handling and neurobehavioral screening of these models. Moreover, we highlight the potential of C. elegans to elucidate the in-vivo mechanisms of neuron-to-neuron protein transfer that may underlie spreading Lewy pathology in PD, and its suitability for in-vitro studies. Given the advantages of C. elegans and microfluidics technology, their integration has the potential to facilitate the investigation of disease pathology and discovery of potential chemical leads for PD.

中文翻译：

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在微流控设备中使用秀丽隐杆线虫模型研究帕金森氏病

帕金森氏病（PD）是与黑质中的多巴胺能神经元（DNs）丢失和α-突触核蛋白（α-syn）蛋白的广泛积累有关的进行性神经系统疾病，导致运动障碍和最终的认知功能障碍。体外细胞培养和体内动物模型提供了研究PD病理学标志并鉴定不同治疗化合物的机会。然而，PD的发病机理和病因还没有被很好地理解，并且尚未发现有效的PD抑制药物。需要生物学上简单但病理相关的疾病模型和先进的筛选技术来揭示支撑蛋白质聚集和PD进展的机制。例如，秀丽隐杆线虫（秀丽隐杆线虫）为基础PD神经行为学研究提供了许多优势，包括简单，映射完善且可访问的神经元系统，与人类的遗传同源性，身体透明性以及对遗传操作的适应性。已经开发出表现出多种PD相关表型的几种转基因蠕虫菌株，以进行神经元和行为测定以及药物筛选。但是，在常规的基于蠕虫的分析中，常用的技术是设备密集型，速度慢和通量低。在过去的二十年中，微流控技术为秀丽隐杆线虫测定的自动化和控制做出了重要贡献。在这篇评论中，我们专注于秀丽隐杆线虫PD模型和用于这些模型的操纵，处理和神经行为筛选的微流体平台的最新进展。此外，我们强调秀丽隐杆线虫阐明神经元到神经元蛋白转移的体内机制的潜力，该机制可能是PD传播路易病理学的基础，并且适用于体外研究。鉴于秀丽隐杆线虫和微流控技术的优势，它们的整合具有促进疾病病理学研究和发现PD潜在化学线索的潜力。