Induction of the unfolded protein response and cell death pathway in Alzheimer's disease, but not in aged Tg2576 mice

Lee, Jin Hwan; Won, Sun Mi; Suh, Jaehong; Son, Sun Joo; Moon, Gyeong Joon; Park, Ui Jin; Gwag, Byoung Joo

doi:10.3858/emm.2010.42.5.040

Cited by 172 publications

(124 citation statements)

References 48 publications

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“…Moreover, CRT is downregulated in cortical neurons of Alzheimer's patient brains (Taguchi et al, 2000) and in striatal neurons of hemiparkinsonian rats (Lessner et al, 2010). Although no functional studies were carried out, it is striking that ER stress is activated in all the above contexts (Wang and Takahashi, 2007;Lee et al, 2010;Lessner et al, 2010). Reductions in CRT may therefore play a general role in neurodegeneration.…”

Section: Discussionmentioning

confidence: 99%

Reduced Calreticulin Levels Link Endoplasmic Reticulum Stress and Fas-Triggered Cell Death in Motoneurons Vulnerable to ALS

Bernard-Marissal

Moumen²,

Sunyach³

et al. 2012

J. Neurosci.

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Cellular responses to protein misfolding are thought to play key roles in triggering neurodegeneration. In the mutant superoxide dismutase (mSOD1) model of amyotrophic lateral sclerosis (ALS), subsets of motoneurons are selectively vulnerable to degeneration. Fast fatigable motoneurons selectively activate an endoplasmic reticulum (ER) stress response that drives their early degeneration while a subset of mSOD1 motoneurons show exacerbated sensitivity to activation of the motoneuron-specific Fas/NO pathway. However, the links between the two mechanisms and the molecular basis of their cellular specificity remained unclear. We show that Fas activation leads, specifically in mSOD1 motoneurons, to reductions in levels of calreticulin (CRT), a calcium-binding ER chaperone. Decreased expression of CRT is both necessary and sufficient to trigger SOD1 G93A motoneuron death through the Fas/NO pathway. In SOD1 G93Amice in vivo, reductions in CRT precede muscle denervation and are restricted to vulnerable motor pools. In vitro, both reduced CRT and Fas activation trigger an ER stress response that is restricted to, and required for death of, vulnerable SOD1 G93A motoneurons. Our data reveal CRT as a critical link between a motoneuron-specific death pathway and the ER stress response and point to a role of CRT levels in modulating motoneuron vulnerability to ALS.

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Section: Discussionmentioning

confidence: 99%

Reduced Calreticulin Levels Link Endoplasmic Reticulum Stress and Fas-Triggered Cell Death in Motoneurons Vulnerable to ALS

Bernard-Marissal

Moumen²,

Sunyach³

et al. 2012

J. Neurosci.

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“…Apart from that, activation of PDI during ER stress was described so far in plants and in brain tissue of mice with Alzheimer disease. 39,40 These reports have not addressed the question of whether the 55 kDa or the 200 kDa (or both) represent the active PDI form. Studying the leukemic cell lines HL60 and U937, we found that ER stress preferentially induced the oligomeric 200-kDa PDI complex paralleled by a decrease in CEBPA protein.…”

Section: Discussionmentioning

confidence: 99%

Protein disulfide isomerase blocks CEBPA translation and is up-regulated during the unfolded protein response in AML

Haefliger

Klebig

Schaubitzer

et al. 2011

Blood

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“…Angiotensin II receptor blockade decreases dopaminergic cell death caused by 6-OHDA by down-regulating CHOP expression (Wu et al 2013). In addition to PD, CHOP expression is also markedly induced in brains from mice with AD (Lee et al 2010a). Silencing of CHOP in the rabbit hippocampus protects animals from AD induced by 27-hydroxycholesterol, an oxidized metabolite of cholesterol (Prasanthi et al 2011).…”

Section: Chop/ddit3/gadd153mentioning

confidence: 99%

Physiological/pathological ramifications of transcription factors in the unfolded protein response

2017

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Numerous environmental, physiological, and pathological insults disrupt protein-folding homeostasis in the endoplasmic reticulum (ER), referred to as ER stress. Eukaryotic cells evolved a set of intracellular signaling pathways, collectively termed the unfolded protein response (UPR), to maintain a productive ER protein-folding environment through reprogramming gene transcription and mRNA translation. The UPR is largely dependent on transcription factors (TFs) that modulate expression of genes involved in many physiological and pathological conditions, including development, metabolism, inflammation, neurodegenerative diseases, and cancer. Here we summarize the current knowledge about these mechanisms, their impact on physiological/pathological processes, and potential therapeutic applications.

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Induction of the unfolded protein response and cell death pathway in Alzheimer's disease, but not in aged Tg2576 mice

Cited by 172 publications

References 48 publications

Reduced Calreticulin Levels Link Endoplasmic Reticulum Stress and Fas-Triggered Cell Death in Motoneurons Vulnerable to ALS

Reduced Calreticulin Levels Link Endoplasmic Reticulum Stress and Fas-Triggered Cell Death in Motoneurons Vulnerable to ALS

Protein disulfide isomerase blocks CEBPA translation and is up-regulated during the unfolded protein response in AML

Physiological/pathological ramifications of transcription factors in the unfolded protein response

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