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Prion protein and aging

Posted November 16, 2014
This news or article is intended for readers with certain scientific or professional knowledge in the field.

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.

Full text: PubMed

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