Esposito Sonia, Masala Alessandra, Sanna Simona, Rassu Mauro, Pimxayvong Viengsavanh, Iaccarino Ciro, Crosio Claudia
Rev Neurosci. 2017 Feb 1;28(2):133-144. doi: 10.1515/revneuro-2016-0041.
Redox processes are key events in the degenerative cascade of many adult-onset neurodegenerative diseases (NDs), but the biological relevance of a single redox change is often dependent on the redox couple involved and on its subcellular origin. The biosensors based on engineered fluorescent proteins (redox-sensitive GFP [roGFP]) offer a unique opportunity to monitor redox changes in both physiological and pathological contexts in living animals and plants. Here, we review the use of roGFPs to monitor oxidative stress in different three adult-onset NDs: Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS). Despite the many differences spanning from incidence to onset, the hypotheses on biological processes underlying both sporadic and familiar ND forms in humans outline a model in which noncompeting mechanisms are likely to converge in various unsuccessful patterns to mediate the selective degeneration of a specific neuronal population. roGFPs, targeted to different cell compartments, are successfully used as specific markers of cell toxicity, induced by expression of causative genes linked to a determined ND. We also report the use of roGFP to monitor oxidative stress induced by the expression of the ALS-causative gene SOD1.
氧化还原过程是许多成人发病的神经退行性疾病（NDs）退行性级联反应中的关键事件，但单一氧化还原变化的生物学相关性通常取决于所涉及的氧化还原对及其亚细胞起源。基于工程荧光蛋白的生物传感器（氧化还原敏感型绿色荧光蛋白[roGFP]）为监测活体动物和植物生理及病理环境中的氧化还原变化提供了独特的机会。在此，我们综述了利用roGFP监测三种成人发病的NDs（阿尔茨海默病[AD]、帕金森病[PD]和肌萎缩侧索硬化症[ALS]）中氧化应激的情况。尽管从发病率到发病时间存在诸多差异，但关于人类散发性和家族性NDs形式背后生物学过程的假说勾勒出了一个模型：在该模型中，非竞争性机制可能以各种不成功的模式汇聚，介导特定神经元群体的选择性退化。靶向不同细胞区室的roGFP被成功用作由与特定ND相关的致病基因表达所诱导细胞毒性的特异性标志物。我们还报告了利用roGFP监测由ALS致病基因SOD1表达所诱导的氧化应激情况。
