DOI: 10.1111/j.1460-9568.2012.08008.x. The unfolded protein response in models of human mutant G93A amyotrophic lateral sclerosis

The unfolded protein response in models of human mutant G93A amyotrophic lateral sclerosis

10.1111/j.1460-9568.2012.08008.x

Crossref journal-article

Wiley

European Journal of Neuroscience (311)

Abstract

AbstractRecent studies indicate that endoplasmic reticulum (ER) stress is involved in the pathogenesis of familial and sporadic amyotrophic lateral sclerosis (ALS). ER stress occurs when the ER–mitochondria calcium cycle (ERMCC) is disturbed and misfolded proteins accumulate in the ER. To cope with ER stress, the cell engages the unfolded protein response (UPR). While activation of the UPR has been shown in some ALS models and tissues, ER stress elements have not been studied directly in motor neurons. Here we investigated the expression of XBP1 and ATF6α and phosphorylation of eIF2α, and their modulation, in mutated SOD1G93A NSC34 and animal model of ALS. Expression of XBP1 and ATF6α mRNA and protein was enhanced in SOD1G93A NSC34 cells. Activation of ATF6α and XBP1 and phosphorylation of eIF2α were detectable in mutated SOD1G93A motor but not in wild‐type motor neurons. Treatment with the ER stressor thapsigargin enhanced phosphorylation of eIF2α and activated proteolysis of ATF6α and splicing of XBP1 in NSC34 and motor neurons in a time‐dependent manner. The present study thus provides direct evidence of activated UPR in motor neurons which overexpress human pathogenic mutant SOD1G93A, providing evidence that ER stress plays a major role in ALS.

Bibliography

Prell, T., LautenschlÃ¤ger, J., Witte, O. W., Carri, M. T., & Grosskreutz, J. (2012). The unfolded protein response in models of human mutant G93A amyotrophic lateral sclerosis. European Journal of Neuroscience, 35(5), 652â660. Portico.

Authors 5

T. Prell (first)
J. Lautenschläger (additional)
O. W. Witte (additional)
M. T. Carri (additional)
J. Grosskreutz (additional)

References 48 Referenced 41

Dates

Type	When
Created	13 years, 5 months ago (March 6, 2012, 2:13 a.m.)
Deposited	1 year, 10 months ago (Oct. 15, 2023, 4:03 a.m.)
Indexed	1 month, 1 week ago (July 25, 2025, 6:07 a.m.)
Issued	13 years, 6 months ago (March 1, 2012)
Published	13 years, 6 months ago (March 1, 2012)
Published Online	13 years, 6 months ago (March 6, 2012)
Published Print	13 years, 6 months ago (March 1, 2012)

Funders 0

None

BibTeX

@article{Prell_2012, title={The unfolded protein response in models of human mutant G93A amyotrophic lateral sclerosis}, volume={35}, ISSN={1460-9568}, url={http://dx.doi.org/10.1111/j.1460-9568.2012.08008.x}, DOI={10.1111/j.1460-9568.2012.08008.x}, number={5}, journal={European Journal of Neuroscience}, publisher={Wiley}, author={Prell, T. and Lautenschläger, J. and Witte, O. W. and Carri, M. T. and Grosskreutz, J.}, year={2012}, month=mar, pages={652–660} }

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