Laboratory of Prion Biology, Department of Neuroscience, Scuola Internazionale Superiore di Studi Avanzati Trieste, Italy.
Front Cell Dev Biol. 2014 Aug 29;2:44. doi: 10.3389/fcell.2014.00044. eCollection 2014.
The cellular prion protein (PrP(C)) has been widely investigated ever since its conformational isoform, the prion (or PrP(Sc)), was identified as the etiological agent of prion disorders. The high homology shared by the PrP(C)-encoding gene among mammals, its high turnover rate and expression in every tissue strongly suggest that PrP(C) may possess key physiological functions. Therefore, defining PrP(C) roles, properties and fate in the physiology of mammalian cells would be fundamental to understand its pathological involvement in prion diseases. Since the incidence of these neurodegenerative disorders is enhanced in aging, understanding PrP(C) functions in this life phase may be of crucial importance. Indeed, a large body of evidence suggests that PrP(C) plays a neuroprotective and antioxidant role. Moreover, it has been suggested that PrP(C) is involved in Alzheimer disease, another neurodegenerative pathology that develops predominantly in the aging population. In prion diseases, PrP(C) function is likely lost upon protein aggregation occurring in the course of the disease. Additionally, the aging process may alter PrP(C) biochemical properties, thus influencing its propensity to convert into PrP(Sc). Both phenomena may contribute to the disease development and progression. In Alzheimer disease, PrP(C) has a controversial role because its presence seems to mediate β-amyloid toxicity, while its down-regulation correlates with neuronal death. The role of PrP(C) in aging has been investigated from different perspectives, often leading to contrasting results. The putative protein functions in aging have been studied in relation to memory, behavior and myelin maintenance. In aging mice, PrP(C) changes in subcellular localization and post-translational modifications have been explored in an attempt to relate them to different protein roles and propensity to convert into PrP(Sc). Here we provide an overview of the most relevant studies attempting to delineate PrP(C) functions and fate in aging.
自从朊病毒（或 PrP(Sc)）被鉴定为朊病毒病的病因以来，细胞朊蛋白 (PrP(C)) 就一直受到广泛研究。哺乳动物中 PrP(C) 编码基因的高度同源性、高周转率和在所有组织中的表达强烈表明 PrP(C) 可能具有关键的生理功能。因此，定义 PrP(C) 在哺乳动物细胞生理学中的作用、特性和命运对于理解其在朊病毒病中的病理参与至关重要。由于这些神经退行性疾病的发病率在衰老过程中增加，因此了解 PrP(C) 在这一生命阶段的功能可能至关重要。事实上，大量证据表明 PrP(C) 具有神经保护和抗氧化作用。此外，有人提出 PrP(C) 参与了阿尔茨海默病，这是另一种主要在老年人群中发生的神经退行性疾病。在朊病毒病中，PrP(C) 功能可能会在疾病过程中发生蛋白聚集时丧失。此外，衰老过程可能会改变 PrP(C) 的生化特性，从而影响其转化为 PrP(Sc) 的倾向。这两种现象都可能导致疾病的发展和进展。在阿尔茨海默病中，PrP(C) 的作用存在争议，因为其存在似乎介导了β-淀粉样蛋白毒性，而其下调与神经元死亡相关。从不同角度研究了 PrP(C) 在衰老中的作用，经常得出相互矛盾的结果。研究了与记忆、行为和髓鞘维持相关的衰老时 PrP(C) 的潜在蛋白功能。在衰老的小鼠中，研究了亚细胞定位和翻译后修饰的 PrP(C) 变化，试图将其与不同的蛋白作用和转化为 PrP(Sc) 的倾向联系起来。在这里，我们提供了一个概述，试图描绘 PrP(C) 在衰老中的作用和命运。
