Endoplasmic Reticulum Stress Response in Prion Diseases
Pp. 127-135 (9)
Abhisek Mukherjee and Claudio Soto
Prion diseases are infectious neurodegenerative diseases associated with the brain
accumulation of the misfolded prion protein. Despite substantial knowledge of the mechanism of
infection and disease transmission, little is known about the molecular pathways involved in
neurodegeneration. Recent findings implicate endoplasmic reticulum (ER) stress as a key event in
brain dysfunction. The available evidence indicates that accumulation of misfolded prion protein
induces ER stress, followed by the activation of the unfolded protein response. Chronic stress
produced by the sustained formation of misfolded proteins lead to neuronal apoptosis and synaptic
alterations. In this article we discuss the role of ER stress in prion neurodegeneration and the
signaling pathways implicated.
Protein Misfolding Disorders Laboratory, George and Cynthia Mitchell Center for Neurodegenerative Diseases, Dept of Neurology, University of Texas Medical School at Houston.