Inhibition of apoptosis signal-regulating kinase 1 reduces endoplasmic reticulum stress and nuclear huntingtin fragments in a mouse model of Huntington disease

Cho, K.J.; Lee, B.I.; Cheon, So Yeong; Kim, Hyun Woo; Kim, G.W.

doi:10.1016/j.neuroscience.2009.07.048

Cited by 56 publications

(41 citation statements)

References 26 publications

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“…UPR induction was observed by expression of mutant Htt in yeast and mammalian cells [8,32,36,37,44]. It has also been reported in animal models of HD [36,[163][164][165]. P97 depletion by mutant Htt appears to be a major cause in the inhibition of ERAD, which causes ER stress, as p97 overexpression was sufficient for complete compensation in mammalian cells (Fig.…”

Section: Genesis and Impact Of Er Stress In Huntington's Diseasementioning

confidence: 77%

“…Besides the products of the classic UPR-induced genes (ATF6, BiP, protein disulfide isomerase, CHOP, etc), [8,36,44,163,164], other proteins that are induced by ER stress have recently been linked to HD pathology and are upregulated in HD patients, Rrs1 [36] and SCAMP5, the latter especially upregulated in the striatum [164].…”

Section: Genesis and Impact Of Er Stress In Huntington's Diseasementioning

confidence: 99%

“…Apoptotic pathways induced through ER stress have been suggested in HD pathology through induction of CHOP and also of ASK1 [44,163,173,174], leading finally to caspase activation [175]. Mutant Htt causes altered calcium signaling and apoptosis, possibly by its interference with the ER IP3R.…”

Section: Genesis and Impact Of Er Stress In Huntington's Diseasementioning

confidence: 99%

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Genesis of ER stress in Huntington’s Disease

Shenkman

Eiger

Lederkremer

2015

Endoplasmic Reticulum Stress in Diseases

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Recent research has identified ER stress as a major mechanism implicated in cytotoxicity in many neurodegenerative diseases, among them Huntington’s disease. This genetic disorder is of late-onset, progressive and fatal, affecting cognition and movement. There is presently no cure nor any effective therapy for the disease. This review focuses on recent findings that shed light on the mechanisms of the advent and development of ER stress in Huntington’s disease and on its implications, highlighting possible therapeutic avenues that are being or could be explored.

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Section: Genesis and Impact Of Er Stress In Huntington's Diseasementioning

confidence: 77%

Section: Genesis and Impact Of Er Stress In Huntington's Diseasementioning

confidence: 99%

See 1 more Smart Citation

Genesis of ER stress in Huntington’s Disease

Shenkman

Eiger

Lederkremer

2015

Endoplasmic Reticulum Stress in Diseases

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“…The expression of ER stress related markers, including GRP78/BiP, CHOP and HERP, is increased at the mRNA level in postmortem brains of HD patients [59]. The increase of ER stress was also observed in HD mouse models even at the early stage of the disease [59,60]. In addition, altered ER calcium homeostasis was found in HD mouse models [61].…”

Section: Huntington's Diseasementioning

confidence: 96%

“…ASK1 is a key element in ER stress-induced cell death that plays an important role in the neuropathological alterations in polyQ diseases [57]. Inhibition of ASK1 reduces ER stress and nuclear Htt fragments in a mouse model of HD [60]. Down-regulation of RTN3 promotes the clearance of cytoplasmic PrP aggregates and alleviates ER stress, the apoptosis due to the cytoplasmic PrP aggregates is inhibited accordingly, suggesting that RTN3 negatively regulates autophagy to block the clearance of cytoplasmic PrP aggregates and may serve as a target for inducing autophagy to treat prion diseases [72].…”

Section: Therapeutic Implicationsmentioning

confidence: 99%

Roles of Endoplasmic Reticulum Stress in Neurodegenerative Diseases

Wang¹

2012

Transl Med

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The accumulation of misfolded proteins disrupts the functioning of endoplasmic reticulum (ER), leading to induction of the unfolded protein response (UPR) that protect cells against the toxic buildup of such proteins. However, prolonged stress due to the buildup of these toxic proteins induces specific cell death pathways. There is accumulating evidence implicating ER stress in the development and progression of neurodegenerative diseases. With the improved understanding of the underlying molecular mechanisms, therapeutic interventions that target the ER stress response would be potential strategies to treat neurodegenerative diseases.

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The presence of extracellular matrix alters the chondrocyte response to endoplasmic reticulum stress

Nugent

McBurney

Horton

2011

J of Cellular Biochemistry

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The objective of this study was to test the hypothesis that extracellular matrix (ECM) would alter the endoplasmic reticulum (ER) stress response of chondrocytes. Chondrocytes were isolated from calf knees and maintained in monolayer culture or suspended in collagen I to form spot cultures (SCs). Our laboratory has shown that bovine chondrocytes form cartilage with properties similar to native cartilage after 2-4 weeks in SCs. Monolayer cultures treated with ER stressors glucose withdrawal (-Glu), tunicamycin (TN), or thapsigargin (TG) up-regulated Grp78 and Gadd153, demonstrating a complete ER stress response. SCs were grown at specific times from 1 day to 6 weeks before treatment with ER stressors. Additionally, SCs grown for 1, 2, or 6 weeks were treated with increasing concentrations of TN or TG. Western blotting of SCs for Grp78 indicated that increased ECM accumulation results in delayed expression; however, Grp78 mRNA is up-regulated in response to ER stressors even after 6 weeks in culture. SCs treated with ER stressors did not up-regulate Gadd153, suggesting that the cells experienced ER stress but would not undergo apoptosis. In fact, SCs undergo apoptosis upon ER stress treatment after 0-1 day of growth; however, after 4 days and to 6 weeks, apoptosis in treated samples was not different than controls. Pro-survival molecules Bcl-2 and Bag-1 were up-regulated upon ER stress in SCs. These results suggest that presence of ECM confers protection from ER stressors. Future studies involving chondrocyte physiology should focus on responses in conditions more closely mimicking the in vivo cartilage environment.

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Inhibition of apoptosis signal-regulating kinase 1 reduces endoplasmic reticulum stress and nuclear huntingtin fragments in a mouse model of Huntington disease

Cited by 56 publications

References 26 publications

Genesis of ER stress in Huntington’s Disease

Genesis of ER stress in Huntington’s Disease

Roles of Endoplasmic Reticulum Stress in Neurodegenerative Diseases

The presence of extracellular matrix alters the chondrocyte response to endoplasmic reticulum stress

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