RETRACTED: Endoplasmic reticulum stress and induction of the unfolded protein response in human sporadic amyotrophic lateral sclerosis
Authors: Malcolm K Horne
Julie D Atkin
Doris Tomas
Catriona McLean
Manal A Farg
Adam K Walker
Journal: Neurobiology of disease (2008)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords: unfolded protein response; UPR; familial amyotrophic lateral sclerosis; ALS; superoxide dismutase
Affiliations: Howard Florey Institute, University of Melbourne, Parkville, VIC 3010, Australia; Centre for Neuroscience, University of Melbourne, Australia. Electronic address: ., Howard Florey Institute, University of Melbourne, Parkville, VIC 3010, Australia., Howard Florey Institute, University of Melbourne, Parkville, VIC 3010, Australia; Centre for Neuroscience, University of Melbourne, Australia., Anatomical Pathology, Alfred Hospital, Commercial road, Prahan, Victoria, 3181, Australia.

Abstract:  The unfolded protein response (UPR) is induced at symptom onset and disease end stage in rodent models of familial amyotrophic lateral sclerosis (ALS) that express superoxide dismutase (SOD1) mutations. However, ninety percent of human ALS is sporadic and mutations in SOD1 account for only 2% of total ALS. Here we show that a full UPR, including induction of stress sensor kinases, chaperones and apoptotic mediators, is also present in spinal cords of human patients with sporadic disease. Furthermore, the UPR chaperone protein disulphide isomerase (PDI) was present in CSF and was aggregated and widely distributed throughout the motor neurons of these patients. We also show up-regulation of UPR prior to the onset of symptoms in SOD1 rodents, implying an active role in disease. This study offers new insights into pathogenesis, placing ER stress onto a generic pathophysiology for ALS. 

Retracted: Yes

PubPeer comments:
 J Biol Chem 2006 Oct 6;281(40):30152-65 has been retracted PMID: 28710340. The retraction notice states  a portion of the actin immunoblot image from rat lysates in Fig. 2A was inadvertently reused in the mouse lysate panel images in Fig. 2A, in Fig. 2D, and in Fig. 8A. These (rat) actin blots are the same ones that appear in this paper Neurobiology of Disease (2008) pubmed: 18440237 but described as coming from 60 day old mice. , 
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 Figure 1A Western blots have lanes that appear more similar that would be expected. ATF6 panel has only 12 lanes; others have 13. ![file] ![file] , 
 In Fig. 1A there appear to be 14 PERK lanes, but only `13 lanes are labelled. When the first 3 PERK (P)atient samples in Fig 1A are compressed, lightened, and horizontally flipped, they look very similar to the first 3 (Con)trol lanes. ![file] , 
 Retraction statement: This article has been retracted at the request of the authors. The authors became aware of an issue with incorrect loading control images being presented and are now retracting the article in the interests of maintaining their publication standards and those of the journal. The authors maintain that these presentational errors do not impact the underlying scientific findings of the article, some of which have been verified in other laboratories. Fig. 4 contains incorrect loading control images of SOD1G93A mouse. The b-actin images blots presented are SOD1G93A rat b-actin bands that were accidentally used when compiling the image for publication. Similarly, in Fig. 1 the samples were run in two separate experiments with the controls split across the two blots. The b-actin for one set of controls was accidentally used for the second controls. The authors state that quantifications were performed using the correct b-actin bands. In fig. 1, concerns were raised that each of the panels had 13 lanes except for the ATF panel which appeared to have only twelve lanes. The authors state that the ATF6 panel has 13 lanes, but last two control lanes of the gel have no signal, making it difficult to accurately align the end part of the gel correctly for display in the figure. ,