Stressing Out the ER: A Role of the Unfolded Protein Response in Prion-Related Disorders
Claudio A. Hetz and Claudio Soto
Affiliation: Harvard School of Public Health, Department of Immunology and Infectious Diseases, FXB Building, Room 205, 653 Huntington Avenue Boston, MA 02115, USA.
Transmissible Spongiform Encephalopathies are fatal and infectious neurodegenerative diseases characterized by extensive neuronal apoptosis and the accumulation of an abnormally folded form of the cellular prion protein (PrP), denoted PrPSC. Compelling evidence suggests the involvement of several signaling pathways in prion pathogenesis, including proteasome dysfunction, alterations in the protein maturation pathways and the unfolded protein response. Recent reports indicate that endoplasmic reticulum stress due to the PrP misfolding may be a critical factor mediating neuronal dysfunction in prion diseases. These findings have applications for developing novel strategies for treatment and early diagnosis of transmissible spongiform encephalopathies and other neurodegenerative diseases.
Keywords: Prion related disorders, apoptosis, PrPSC, proteasome, ER stress, glucose-regulated proteins, caspase-12, PrPSC-like, aggresomes
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