Title:Modulation of Endoplasmic Reticulum Stress: An Opportunity to Prevent Neurodegeneration?
Volume: 14
Issue: 4
Author(s): Ana I. Placido, Claudia M.F. Pereira, Ana I. Duarte, Emanuel Candeias, Sonia C. Correia, Cristina Carvalho, Susana Cardoso, Catarina R. Oliveira and Paula I. Moreira
Affiliation:
Keywords:
Endoplasmic reticulum, neurodegeneration, therapeutic targets, unfolded protein response.
Abstract: 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.
