National Reference Center for CJD Surveillance, Department of Neurology, University Medical Center, Georg August University, Göttingen, Germany.
Department of Neuroscience, Istituto Superiore di Sanità, Rome, Italy.
Nat Rev Dis Primers. 2024 Feb 29;10(1):14. doi: 10.1038/s41572-024-00497-y.
Prion diseases share common clinical and pathological characteristics such as spongiform neuronal degeneration and deposition of an abnormal form of a host-derived protein, termed prion protein. The characteristic features of prion diseases are long incubation times, short clinical courses, extreme resistance of the transmissible agent to degradation and lack of nucleic acid involvement. Sporadic and genetic forms of prion diseases occur worldwide, of which genetic forms are associated with mutations in PRNP. Human to human transmission of these diseases has occurred due to iatrogenic exposure, and zoonotic forms of prion diseases are linked to bovine disease. Significant progress has been made in the diagnosis of these disorders. Clinical tools for diagnosis comprise brain imaging and cerebrospinal fluid tests. Aggregation assays for detection of the abnormally folded prion protein have a clear potential to diagnose the disease in peripherally accessible biofluids. After decades of therapeutic nihilism, new treatment strategies and clinical trials are on the horizon. Although prion diseases are relatively rare disorders, understanding their pathogenesis and mechanisms of prion protein misfolding has significantly enhanced the field in research of neurodegenerative diseases.
朊病毒病具有共同的临床和病理特征，如海绵状神经元变性和异常形式的宿主蛋白沉积，称为朊病毒蛋白。朊病毒病的特征是潜伏期长、临床病程短、传染性剂对降解的极端抗性以及缺乏核酸参与。散发性和遗传性朊病毒病在全球范围内发生，其中遗传性形式与 PRNP 中的突变有关。这些疾病因医源性暴露而在人与人之间传播，而朊病毒病的人畜共患病形式与牛病有关。这些疾病的诊断取得了重大进展。用于诊断的临床工具包括脑部成像和脑脊液测试。用于检测异常折叠的朊病毒蛋白的聚集测定法具有在可从外周获得的生物流体中诊断该疾病的明显潜力。经过几十年的治疗无效后，新的治疗策略和临床试验即将出现。尽管朊病毒病是相对罕见的疾病，但对其发病机制和朊病毒蛋白错误折叠机制的理解极大地促进了神经退行性疾病研究领域的发展。
