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Updated: Aug 22, 2026

Investigating the Spreading and Toxicity of Prion-like Proteins Using the Metazoan Model Organism C. elegans
Published on: January 8, 2015
Molecular mechanisms of neurotoxicity of pathological prion protein
Joaquin Castilla1, Claudio Hetz, Claudio Soto
1University of Texas Medical Branch, Galveston, TX 77555, USA.
Abstract:
Transmissible Spongiform Encephalopathies or prion related disorders are fatal and infectious neurodegenerative diseases characterized by extensive neuronal apoptosis and accumulation of a misfolded form of the cellular prion protein (PrP), denoted PrP(Sc). Although the mechanism of neurodegeneration and the involvement of PrP(Sc) is far from clear, data indicates that neuronal apoptosis might be related to activation of several signaling pathways, including proteasome dysfunction, alterations in prion maturation pathway and endoplasmic reticulum (ER) stress. In this article we describe recent studies investigating the molecular mechanism of PrP(Sc) neurotoxicity. We propose a model in which the key step in the pathogenesis of prion disorders, independent on their etiology, is the alteration of ER-homeostasis due to drastic modifications of the physicochemical properties of PrP, leading to the activation of ER-dependent signaling pathways that controls cellular survival.
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