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.

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@article{Plcido2015ModulationOE, title={Modulation of endoplasmic reticulum stress: an opportunity to prevent neurodegeneration?}, author={Ana Isabel Pl{\'a}cido and Cl{\'a}udia Maria F. Pereira and Ana I Duarte and Emanuel Monteiro Candeias and S{\'o}nia Catarina Correia and Cristina Isabel Carvalho and Susana Cardoso and Catarina Oliveira and Paula I Moreira}, journal={CNS & neurological disorders drug targets}, year={2015}, volume={14 4}, pages={518-33} }