Modulation of endoplasmic reticulum stress: an opportunity to prevent neurodegeneration?
Neurodegenerative diseases (e.g. Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis and prion-related diseases) have in common the presence of protein aggregates in specific brain areas where significant neuronal loss is detected. In these pathologies, accumulating evidence supports a close correlation between neurodegeneration and endoplasmic reticulum (ER) stress, a condition that arises from ER lumen overload with misfolded proteins. Under these conditions, ER stress sensors initiate the unfolded protein response to restore normal ER function. If stress is too prolonged, or adaptive responses fail, apoptotic cell death ensues. Therefore, it was recently suggested that the manipulation of the ER unfolded protein response could be an effective strategy to avoid neuronal loss in neurodegenerative disorders. We will review the mechanisms underlying ER stress-associated neurodegeneration and discuss the possibility of ER as a therapeutic target.
Ana I
AI
Placido
Claudia M F
CM
Pereira
Ana I
AI
Duarte
Emanuel
E
Candeias
Sonia C
SC
Correia
Cristina
C
Carvalho
Susana
S
Cardoso
Catarina R
CR
Oliveira
Institute of Physiology - Faculty of Medicine, University of Coimbra & CNC - Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal. venta@ci.uc.pt.
Paula I
PI
Moreira
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001921:Brain / Q000378:metabolism*; D059865:Endoplasmic Reticulum Stress / Q000502:physiology*; D006801:Humans; D019636:Neurodegenerative Diseases / Q000378:metabolism* / Q000517:prevention & control; D018384:Oxidative Stress / Q000502:physiology*; D017510:Protein Folding; D015398:Signal Transduction / Q000502:physiology