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Updated: Sep 20, 2026

Interview: Protein Folding and Studies of Neurodegenerative Diseases
Published on: July 16, 2008
'Unfolding' pathways in neurodegenerative disease
Mark S Forman1, Virginia M-Y Lee, John Q Trojanowski
1Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, University of Pennsylvania, 3600 Spruce Street, Maloney Building, 3rd Floor, Philadelphia, PA 19104, USA. formanm@mail.med.upenn.edu
Abstract:
The endoplasmic reticulum responds to stress by initiating a cascade of events known as the 'unfolded-protein response' (UPR). The accumulation of misfolded proteins in the leukodystrophy Pelizaeus-Merzbacher disease activates this stress response, resulting in apoptosis of oligodendrocytes. Although it remains uncertain whether the UPR plays a mechanistic role in prototypical neurodegenerative disorders such as Alzheimer's disease, this is plausible because misfolded proteins are directly implicated in the pathogenesis of these disorders.
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