Protein folding stress in neurodegenerative diseases: a glimpse into the ER
Several neurodegenerative diseases share common neuropathology, primarily featuring the presence in the brain of abnormal protein inclusions containing specific misfolded proteins. Recent evidence indicates that alteration in organelle function is a common pathological feature of protein misfolding disorders, highlighting perturbations in the homeostasis of the endoplasmic reticulum (ER). Signs of ER stress have been detected in most experimental models of neurological disorders and more recently in brain samples from human patients with neurodegenerative disease. To cope with ER stress, cells activate an integrated signaling response termed the unfolded protein response (UPR), which aims to reestablish homeostasis in part through regulation of genes involved in protein folding, quality control and degradation pathways. Here we discuss the particular mechanisms currently proposed to be involved in the generation of protein folding stress in different neurodegenerative conditions and speculate about possible therapeutic interventions.
Artículo de publicación ISI
FONDECYT 1100176 FONDAP 15010006 Millennium Nucleus P07-048-F CHDI Foundation Inc Genzyme Alzheimer's Association NIRG-10-173294 M.J. Fox Foundation for Parkinson's Research ICGEB ALSA-The Milton Safenowitz Post-Doctoral Fellowship for ALS Research 1829 CONICYT 79100007 National Institutes of Health AI32412 Mathers Foundation
DOI: DOI: 10.1016/j.ceb.2011.01.003
Quote ItemCURRENT OPINION IN CELL BIOLOGY Volume: 23 Issue: 2 Pages: 239-252 Published: APR 2011