Document Detail


Endoplasmic reticulum stress and the ER mitochondrial calcium cycle in amyotrophic lateral sclerosis.
MedLine Citation:
PMID:  22292840     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
Abstract The endoplasmic reticulum (ER) is a multifunctional organelle involved in protein synthesis, processing and folding, in intracellular transport and calcium signalling. ER stress can be triggered by depletion of ER calcium content and the accumulation of un- and mis-folded proteins, and relays stress signals to the ER mitochondria calcium cycle (ERMCC) and to the nucleus and protein translation machinery. The ensuing unfolded protein response (UPR) helps to cope with ER stress. Total protein synthesis is inhibited to keep protein load low, while the synthesis of ER chaperones, which assist protein folding, is induced. If cell integrity cannot be restored, signal cascades mediating cell death are activated. This review focuses on the role of ER stress and the UPR in the pathology of amyotrophic lateral sclerosis (ALS). The triggers for ER stress are as yet unclear, but induction of UPR sensor proteins, up-regulation of chaperones and induction of cell death proteins have been described in human post mortem ALS tissue and in mutant superoxide dismutase-1 (SOD1) expressing models of ALS. TDP-43 and VAPB seem to be involved in UPR signalling as well. Recent reports raise hope that UPR sensor proteins become effective therapeutic targets in the treatment of ALS.
Authors:
Janin Lautenschlaeger; Tino Prell; Julian Grosskreutz
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Amyotrophic lateral sclerosis : official publication of the World Federation of Neurology Research Group on Motor Neuron Diseases     Volume:  13     ISSN:  1471-180X     ISO Abbreviation:  Amyotroph Lateral Scler     Publication Date:  2012 Feb 
Date Detail:
Created Date:  2012-02-01     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101283386     Medline TA:  Amyotroph Lateral Scler     Country:  England    
Other Details:
Languages:  eng     Pagination:  166-77     Citation Subset:  IM    
Affiliation:
Hans-Berger Department of Neurology, Friedrich-Schiller-University Hospital Jena , Jena , Germany.
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