'Unfolding' pathways in neurodegenerative disease.
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.
Forman
Mark S
MS
Center 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
Lee
Virginia M-Y
VM
Trojanowski
John Q
JQ
D000222:Adaptation, Physiological; D000544:Alzheimer Disease / Q000503:physiopathology; D000818:Animals; D017209:Apoptosis; D004721:Endoplasmic Reticulum / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D008565:Membrane Proteins / Q000502:physiology; D051379:Mice; D019636:Neurodegenerative Diseases / Q000503:physiopathology*; D010300:Parkinson Disease / Q000503:physiopathology; D020371:Pelizaeus-Merzbacher Disease / Q000503:physiopathology; D011487:Protein Conformation; D017510:Protein Folding; D013312:Stress, Physiological / Q000503:physiopathology*
D008565:Membrane Proteins