Bacınoğlu Merve Begüm, Bufano Giuseppe, Cazzaniga Federico Angelo, Zanusso Gianluigi, Legname Giuseppe, Moda Fabio
Unit of Laboratory Medicine, Laboratory of Clinical Pathology, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy.
Department of Neuroscience, Biomedicine and Movement Sciences, Università degli Studi di Verona, Verona, Italy.
Subcell Biochem. 2025;112:245-268. doi: 10.1007/978-3-031-97055-9_11.
Prion diseases (PrDs) are fatal neurodegenerative disorders characterized by the accumulation of misfolded prion protein (PrP) in the central nervous system (CNS). This pathological isoform of the cellular prion protein drives disease pathogenesis through its unique ability to propagate itself via a template-directed misfolding mechanism. The definite diagnosis of PrDs relies on the detection of PrP in the CNS by invasive procedures or postmortem examination, limiting early detection and antemortem diagnostic investigations. Real-time quaking-induced conversion (RT-QuIC) has emerged as a revolutionary diagnostic tool, allowing ultrasensitive detection of PrP in cerebrospinal fluid (CSF) and other easily accessible tissues, including the olfactory mucosa, skin, and, more recently, tears. This assay exploits the autocatalytic amplification of misfolded prions, providing high sensitivity and specificity in the detection of peripheral PrP. This chapter explores the advancements and applications of RT-QuIC in diagnosing human PrDs.
朊病毒病（PrDs）是致命的神经退行性疾病，其特征是错误折叠的朊病毒蛋白（PrP）在中枢神经系统（CNS）中积累。细胞朊病毒蛋白的这种病理异构体通过其独特的能力，即通过模板导向的错误折叠机制自我繁殖，来驱动疾病的发病机制。朊病毒病的明确诊断依赖于通过侵入性程序或死后检查在中枢神经系统中检测PrP，这限制了早期检测和生前诊断研究。实时震颤诱导转化（RT-QuIC）已成为一种革命性的诊断工具，能够超灵敏地检测脑脊液（CSF）和其他易于获取的组织中的PrP，包括嗅黏膜、皮肤，以及最近发现的眼泪。该检测方法利用了错误折叠朊病毒的自催化扩增，在外周PrP的检测中提供了高灵敏度和特异性。本章探讨了RT-QuIC在诊断人类朊病毒病方面的进展和应用。
