The function of the cellular prion protein in health and disease

Abstract

The essential role of the cellular prion protein (PrP) in prion disorders such as Creutzfeldt-Jakob disease is well documented. Moreover, evidence is accumulating that PrP may act as a receptor for protein aggregates and transduce neurotoxic signals in more common neurodegenerative disorders, such as Alzheimer's disease. Although the pathological roles of PrP have been thoroughly characterized, a general consensus on its physiological function within the brain has not yet been established. Knockout studies in various organisms, ranging from zebrafish to mice, have implicated PrP in a diverse range of nervous system-related activities that include a key role in the maintenance of peripheral nerve myelination as well as a general ability to protect against neurotoxic stimuli. Thus, the function of PrP may be multifaceted, with different cell types taking advantage of unique aspects of its biology. Deciphering the cellular function(s) of PrP and the consequences of its absence is not simply an academic curiosity, since lowering PrP levels in the brain is predicted to be a powerful therapeutic strategy for the treatment of prion disease. In this review, we outline the various approaches that have been employed in an effort to uncover the physiological and pathological functions of PrP. While these studies have revealed important clues about the biology of the prion protein, the precise reason for PrP's existence remains enigmatic.

Synthetic surfactants with SP‐B and SP‐C analogues to enable worldwide treatment of neonatal respiratory distress syndrome and other lung diseases

“…However, these mice develop pneumonitis-like pathology over time and are more susceptible than wild-type mice to experimental infections [152][153][154][155]. The situation for SP-C is thus reminiscent to what has been observed for amyloid-forming proteins Ab and the prion protein; mutations that promote aggregation into insoluble deposits is detrimental, whilst the precise reasons for their existence remain enigmatic [156,157].…”

Sensing α‐Synuclein From the Outside via the Prion Protein: Implications for Neurodegeneration

“…More recently, PrP C was identified as a possible sensor for αSyn aggregates . In addition to interacting with αSyn and amyloid‐β (Aβ), it was recently proposed that PrP C might act as a conformation‐specific sensor for disease‐associated proteins, suggesting a more general role in the pathogenesis of various neurodegenerative diseases . This remains to be further validated, but could prove to be highly relevant as a target for intervention.…”

“…PrP C is a glycosylphosphatidylinositol‐anchored cell‐surface protein encoded by the Prnp gene and is highly expressed throughout the central nervous system in neurons and astrocytes . Ablation of the Prnp gene in mice induces mild phenotypic alterations . However, these animals are completely resistant to PrP Sc , revealing the essential role of PrP C in the pathogenesis of prion diseases …”

Analysis of the electrophoretic profiles of prion protein in carcinous and pericarcinous lysates of six different types of cancers

“…In this theory, the normal and physiological form of PrP (PrP C ) converts to abnormal and pathological isoform, leading to a pathogenesis of special neurodegenerative disease with markedly short clinical course and 100% fatal rate [1]. As a conservative cellular protein, the have been proposed, such as cell signal transduction, cellular copper metabolism, cell adhesion, anti-apoptosis, migration, immune modulation and cell differentiation [2]. However, depletion of PrP expression in the knock out transgenic mouse does not affect the development and function of central nerve system and even life span [3].…”