Background α-Synuclein is a small soluble protein, whose physiological function in the healthy brain is poorly understood. Intracellular inclusions of α-synuclein, referred to as Lewy bodies (LBs), are pathological hallmarks of α-synucleinopathies, such as Parkinson's disease (PD) or dementia with Lewy bodies (DLB). Main body Understanding of the molecular basis as well as the factors or conditions promoting α-synuclein misfolding and aggregation is an important step towards the comprehension of pathological mechanism of α-synucleinopathies and for the development of efficient therapeutic strategies. Based on the conversion and aggregation mechanism of α-synuclein, novel diagnostic tests, such as protein misfolding seeded conversion assays, e.g. the real-time quaking-induced conversion (RT-QuIC), had been developed. In diagnostics, α-synuclein RT-QuIC exhibits a specificity between 82 and 100% while the sensitivity varies between 70 and 100% among different laboratories. In addition, the α-synuclein RT-QuIC can be used to study the α-synuclein-seeding-characteristics of different α-synucleinopathies and to differentiate between DLB and PD. Conclusion The variable diagnostic accuracy of current α-synuclein RT-QuIC occurs due to different protocols, cohorts and material etc.. An impact of micro-environmental factors on the α-synuclein aggregation and conversion process and the occurrence and detection of differential misfolded α-synuclein types or strains might underpin the clinical heterogeneity of α-synucleinopathies.

中文翻译：

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微环境对α-突触核蛋白转化的影响及其在种子转化试验中的意义。

背景α-突触核蛋白是一种小的可溶性蛋白，人们对其在健康大脑中的生理功能了解甚少。α-突触核蛋白的细胞内包裹体，称为路易体（LB），是α-突触核病的病理标志，例如帕金森氏病（PD）或路易体痴呆（DLB）。主体了解分子基础以及促进α-突触核蛋白错误折叠和聚集的因素或条件，是理解α-突触核蛋白病的病理机制和发展有效治疗策略的重要一步。基于α-突触核蛋白的转化和聚集机制，已经开发了新的诊断测试，例如蛋白质错误折叠接种转化试验，例如实时地震诱导的转化（RT-QuIC）。在诊断中，在不同实验室中，α-突触核蛋白RT-QuIC的特异性在82％至100％之间，而灵敏度在70％至100％之间变化。此外，α-突触核蛋白RT-QuIC可用于研究不同α-突触核蛋白病的α-突触核蛋白播种特性，并区分DLB和PD。结论当前的α-突触核蛋白RT-QuIC的诊断准确性因协议，队列和材料等的不同而发生。微环境因素对α-突触核蛋白的聚集和转化过程以及差异错折叠α的发生和检测产生影响。 -突触核蛋白的类型或菌株可能会增强α-突触核蛋白病的临床异质性。α-突触核蛋白RT-QuIC可用于研究不同α-突触核蛋白病的α-突触核蛋白播种特性，并区分DLB和PD。结论当前的α-突触核蛋白RT-QuIC的诊断准确性因协议，队列和材料等的不同而发生。微环境因素对α-突触核蛋白的聚集和转化过程以及差异错折叠α的发生和检测产生影响。 -突触核蛋白的类型或菌株可能会增强α-突触核蛋白病的临床异质性。α-突触核蛋白RT-QuIC可用于研究不同α-突触核蛋白病的α-突触核蛋白播种特性，并区分DLB和PD。结论当前的α-突触核蛋白RT-QuIC的诊断准确性因协议，队列和材料等的不同而发生。微环境因素对α-突触核蛋白的聚集和转化过程以及差异错折叠α的发生和检测产生影响。 -突触核蛋白的类型或菌株可能会增强α-突触核蛋白病的临床异质性。