蛋白质体外扩增技术在神经退行性疾病诊断中的应用

Application of protein amplification in vitro in the diagnosis of neurodegenerative diseases

神经退行性疾病患者被诊断时通常已经处于疾病晚期,该类疾病的诊断主要取决于临床症状的鉴别,给诊断造成一定的困难。目前已经逐渐开始尝试对神经退行性疾病进行早期诊断。蛋白质体外扩增技术包括蛋白质错误折叠循环扩增(Protein Misfolding Cyclic Amplification, PMCA)和实时震动诱导转化(Real-time Quaking-induced Conversion, RT-QuIC),是用于检测错误折叠的蛋白质聚集体的超灵敏蛋白质扩增法。随着该类技术不断地改进,目前已逐渐应用于朊病毒病、突触核蛋白病、阿尔茨海默病和皮克氏病等疾病中错误折叠蛋白的检测。PMCA和RT-QuIC技术在临床症状出现前的早期阶段也显示出很高的检测灵敏度和特异性,并且可以进行鉴别诊断,这两种检测手段作为实验室辅助诊断方法,具有巨大的应用前景。

Patients with neurodegenerative diseases are usually in the end stage when they are diagnosed. The diagnosis of these diseases mainly depends on the differentiation of clinical symptoms, which causes certain difficulties in diagnosis. In the past few years, some new diagnostic approaches have been developed for the early diagnosis of neurodegenerative diseases.Protein misfolding cyclic amplification(PMCA) and real-time quaking-induced conversion(RT-QuIC) are ultra-sensitive protein amplification assays for the detection of misfolded protein aggregates. With the improvement of these technologies, it has been gradually applied to detect the misfolded proteins in prion disease, synuclein disease, Alzheimer’s disease and Pick’s disease. PMCA and RT-QuIC have also shown high sensitivity and specificity in the pre-clinical stages, and can be used for differential diagnosis. As laboratory auxiliary diagnostic methods, PMCA and RT-QuIC have great application prospects.