Neurobiochemistry, Adolf-Butenandt Institute, Ludwig Maximilians University Munich, Munich, Germany.
Neurodegener Dis. 2012;10(1-4):298-300. doi: 10.1159/000332596. Epub 2011 Dec 9.
Prion diseases in humans and animals comprise a group of invariably fatal neurodegenerative diseases characterized by the formation of a pathogenic protein conformer designated PrP(Sc) and infectious particles denoted prions. The cellular prion protein (PrP(C)) has a central role in the pathogenesis of prion disease. First, it is the precursor of PrP(Sc) and infectious prions and second, its expression on neuronal cells is required to mediate toxic effects of prions. To specifically study the role of PrP(C) as a mediator of toxic signaling, we have developed novel cell culture models, including primary neurons prepared from PrP-deficient mice. Using these approaches we have been able to show that PrP(C) can interact with and mediate toxic signaling of various β-sheet-rich conformers of different origins, including amyloid β, suggesting a pathophysiological role of the prion protein beyond prion diseases.
人类和动物的朊病毒病包括一组具有传染性的致死性神经退行性疾病，其特征是形成一种致病蛋白构象，称为 PrP(Sc) 和传染性颗粒，称为朊病毒。细胞朊蛋白 (PrP(C)) 在朊病毒病的发病机制中起着核心作用。首先，它是 PrP(Sc) 和传染性朊病毒的前体，其次，它在神经元细胞上的表达对于介导朊病毒的毒性作用是必需的。为了专门研究 PrP(C) 作为毒性信号转导介质的作用，我们开发了新型细胞培养模型，包括从小鼠中制备的 PrP 缺陷型神经元。使用这些方法，我们已经能够证明 PrP(C) 可以与各种源自不同来源的富含β-折叠的构象相互作用并介导其毒性信号转导，包括淀粉样β，提示朊病毒蛋白在朊病毒病之外具有病理生理学作用。
