儿茶酚四氢异喹啉增强a-突触核蛋白聚集并指定对多巴胺能神经元的神经毒性

Zixuan Chen, Jian-jun Lu, Jinyan Duan, Xiaotong Zheng, Yanyan Zhang, Chao Han, Yulin Deng
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摘要

帕金森病(PD)是继阿尔茨海默病之后第二大最常见的神经退行性疾病,目前尚无明确的神经保护疗法。先前的研究表明儿茶酚四氢异喹啉(CTIQs)对多巴胺能神经元具有毒性。这些毒素可诱导线粒体功能障碍,从而导致帕金森病的发病。与农用化学品和MPTP等外源性神经毒素不同,CTIQs可以根据多巴胺和特定的醛在人脑中合成。此外,聚集的α-突触核蛋白(α-syn)是PD的标志之一,已被证明是PD发展的关键因素,可受多种神经毒素的影响。有研究表明,CTIQs可增强α-syn的聚集,增加α-syn的神经毒素,这可能是PD的病理机制。因此,本章将揭示CTIQs和α-syn的作用,并试图澄清它们之间的关系。
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Catechol Tetrahydroisoquinolines Enhance a-Synuclein Aggregation andSpecify the Neurotoxicity to Dopaminergic Neurons
Parkinson disease (PD) is the second most common neurodegenerative disorder after Alzheimer disease with no definitive neuroprotective therapies. Previous studies have demonstrated that Catechol tetra hydroisoquinolines (CTIQs) are toxic to dopaminergic neurons. These toxins can induce mitochondrial dysfunction, which consequently contributes to the pathogenesis of PD. Unlike external neurotoxins, such as agrochemicals and MPTP, CTIQs can be synthesized in the brains of human based on the dopamine and the particular aldehyde. Besides, aggregated α-synuclein (α-syn), one of the hallmarks of PD, has been proved to be a key contributor in the development of PD and can be affected by many neurotoxins. Some studies have presented that CTIQs enhanced the aggregation of α-syn and increased the neurotoxin of α-syn, which might be the pathological mechanism of PD. Therefore, this chapter will reveal the role of CTIQs and α-syn and try to clarify the relationship between them.
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