Department of Neurology, University of Kansas Medical Center, Kansas City, KS 66160, USA.
Cells. 2021 Feb 16;10(2):407. doi: 10.3390/cells10020407.
Parkinson's disease (PD) is the second most common neurodegenerative disease, afflicting ~10 million people worldwide. Although several genes linked to PD are currently identified, PD remains primarily an idiopathic disorder. Neuronal protein α-synuclein is a major player in disease progression of both genetic and idiopathic forms of PD. However, it cannot alone explain underlying pathological processes. Recent studies demonstrate that many other risk factors can accelerate or further worsen brain dysfunction in PD patients. Several PD models, including non-mammalian eukaryotic organisms, have been developed to identify and characterize these factors. This review discusses recent findings in three PD model organisms, i.e., yeast, Drosophila, and , that opened new mechanisms and identified novel contributors to this disorder. These non-mammalian models share many conserved molecular pathways and cellular processes with humans. New players affecting PD pathogenesis include previously unknown genes/proteins, novel signaling pathways, and low molecular weight substances. These findings might respond to the urgent need to discover novel drug targets for PD treatment and new biomarkers for early diagnostics of this disease. Since the study of neurodegeneration using simple eukaryotic organisms brought a huge amount of information, we include only the most recent or the most important relevant data.
帕金森病(PD)是第二常见的神经退行性疾病,影响全球约 1000 万人。尽管目前已经确定了几个与 PD 相关的基因,但 PD 仍然主要是一种特发性疾病。神经元蛋白α-突触核蛋白是遗传和特发性 PD 两种形式疾病进展的主要参与者。然而,它本身并不能解释潜在的病理过程。最近的研究表明,许多其他风险因素可以加速或进一步恶化 PD 患者的脑功能障碍。已经开发了几种 PD 模型,包括非哺乳动物真核生物,以鉴定和表征这些因素。本文综述了三种 PD 模式生物(酵母、果蝇和秀丽隐杆线虫)的最新发现,这些发现揭示了该疾病的新机制和新的致病因素。这些非哺乳动物模型与人类具有许多保守的分子途径和细胞过程。影响 PD 发病机制的新参与者包括以前未知的基因/蛋白质、新的信号通路和低分子量物质。这些发现可能有助于满足发现 PD 治疗新靶点和该疾病早期诊断新生物标志物的迫切需求。由于使用简单真核生物研究神经退行性变带来了大量信息,我们仅包括最近或最重要的相关数据。