Targeting the unfolded protein response in disease

Hetz, Claudio; Chevet, Éric; Harding, Heather P.

doi:10.1038/nrd3976

Nat Rev Drug Discov

2013

DOI: 10.1038/nrd3976

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Targeting the unfolded protein response in disease

Claudio Hetz

¹

,

Éric Chevet

²

,

Heather P. Harding

³

Abstract: Stress induced by the accumulation of unfolded proteins in the endoplasmic reticulum (ER) is a feature of specialized secretory cells and is also observed in many diseases, including cancer, diabetes, autoimmune conditions, liver disorders, obesity and neurodegenerative disorders. Cellular adaptation to ER stress is achieved by the activation of the unfolded protein response, which is an integrated signal transduction pathway that modulates many aspects of ER physiology. When these mechanisms of adaptation are… Show more

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Cited by 868 publications

(815 citation statements)

References 187 publications

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“…Our microarray data showed UPR activation specifically in GM1‐NPCs (see supplementary material, Figure S2). Expression levels of many UPR components were altered, in accordance with previous reports . Notably, UPR was not clearly stimulated in GM1 fibroblasts or in GM1‐iPSCs.…”

Section: Resultssupporting

confidence: 90%

A novel human model of the neurodegenerative disease GM1 gangliosidosis using induced pluripotent stem cells demonstrates inflammasome activation

Son

¹

,

Seol

²

,

Lee

³

et al. 2015

The Journal of Pathology

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Exaggerated anticipatory anxiety is common in social anxiety disorder (SAD). Neuroimaging studies have revealed altered neural activity in response to social stimuli in SAD, but fewer studies have examined neural activity during anticipation of feared social stimuli in SAD. The current study examined the time course and magnitude of activity in threat processing brain regions during speech anticipation in socially anxious individuals and healthy controls (HC). Method Participants (SAD n = 58; HC n = 16) underwent functional magnetic resonance imaging (fMRI) during which they completed a 90s control anticipation task and 90s speech anticipation task.

“…Our microarray data showed UPR activation specifically in GM1‐NPCs (see supplementary material, Figure S2). Expression levels of many UPR components were altered, in accordance with previous reports . Notably, UPR was not clearly stimulated in GM1 fibroblasts or in GM1‐iPSCs.…”

Section: Resultssupporting

confidence: 90%

A novel human model of the neurodegenerative disease GM1 gangliosidosis using induced pluripotent stem cells demonstrates inflammasome activation

Son

¹

,

Seol

²

,

Lee

³

et al. 2015

The Journal of Pathology

Get access via publisher Add to collection Cite

Exaggerated anticipatory anxiety is common in social anxiety disorder (SAD). Neuroimaging studies have revealed altered neural activity in response to social stimuli in SAD, but fewer studies have examined neural activity during anticipation of feared social stimuli in SAD. The current study examined the time course and magnitude of activity in threat processing brain regions during speech anticipation in socially anxious individuals and healthy controls (HC). Method Participants (SAD n = 58; HC n = 16) underwent functional magnetic resonance imaging (fMRI) during which they completed a 90s control anticipation task and 90s speech anticipation task.

“…Similarly, a plethora of IRE-1 RNase inhibitors (eg, 4μ8C and STF-083010) are used for anticancer therapy because of their ability to induce apoptosis. 44 Although functional evidence of IRE-1 in the heart is not available, a previous study in cardiac XBP-1s overexpression mice ascertained a protective role of XBP-1s in combating ischemia and reperfusion injury, 45 which supports our data.…”

Section: Discussionsupporting

confidence: 86%

Pak2 as a Novel Therapeutic Target for Cardioprotective Endoplasmic Reticulum Stress Response

Binder

¹

,

Wang

²

,

Radu

³

et al. 2019

Circulation Research

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Exaggerated anticipatory anxiety is common in social anxiety disorder (SAD). Neuroimaging studies have revealed altered neural activity in response to social stimuli in SAD, but fewer studies have examined neural activity during anticipation of feared social stimuli in SAD. The current study examined the time course and magnitude of activity in threat processing brain regions during speech anticipation in socially anxious individuals and healthy controls (HC). Method Participants (SAD n = 58; HC n = 16) underwent functional magnetic resonance imaging (fMRI) during which they completed a 90s control anticipation task and 90s speech anticipation task.

“…Additionally, both the transcript and protein levels of MANF-1 increased in response to ER stress, which is consistent with studies in other systems [9,[48][49][50][51]. As ER-UPR activation helps cells to manage stress through multiple mechanisms, including enhanced protein folding and clearance of nonfunctional proteins [7,52], we examined whether manf-1 mutant animals have defects in these processes. The results showed increased protein aggregation in PD and HD models that express human α-Synuclein and polyQ, respectively.…”

Section: Discussionsupporting

confidence: 81%

Neurotrophic factor MANF regulates autophagy and lysosome function to promote proteostasis in C. elegans

Taylor

¹

,

Hartman

²

,

Gupta

³

2023

Preprint

Get access via publisher Add to collection Cite

Exaggerated anticipatory anxiety is common in social anxiety disorder (SAD). Neuroimaging studies have revealed altered neural activity in response to social stimuli in SAD, but fewer studies have examined neural activity during anticipation of feared social stimuli in SAD. The current study examined the time course and magnitude of activity in threat processing brain regions during speech anticipation in socially anxious individuals and healthy controls (HC). Method Participants (SAD n = 58; HC n = 16) underwent functional magnetic resonance imaging (fMRI) during which they completed a 90s control anticipation task and 90s speech anticipation task.

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