Molecular Mechanisms of Neurotoxicity of Pathological Prion Protein

Title: Molecular Mechanisms of Neurotoxicity of Pathological Prion Protein

Volume: 4 Issue: 4

Author(s): Joaquin Castilla, Claudio Hetz and Claudio Soto

Affiliation:

Keywords: Neurotoxicity, Spongiform Encephalopathies, endoplasmic reticulum (ER), PrPSc

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 PrPSc. Although the mechanism of neurodegeneration and the involvement of PrPSc 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 PrPSc 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.

Cite this article as:

Castilla Joaquin, Hetz Claudio and Soto Claudio, Molecular Mechanisms of Neurotoxicity of Pathological Prion Protein, Current Molecular Medicine 2004; 4 (4) . https://dx.doi.org/10.2174/1566524043360654