ER stress is described as a consequence of disrupted ER homeostasis that activates unfolded protein response pathways. In the review abstract, it is positioned as a major driver of DKD pathology.
First-pass extracted concept
endoplasmic reticulum stress
Candidate: concept label6 source documents20 linked claims
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Aliases
ERS, ER stress
Extracted Explainers
What the tool is doing
What problem it solves
What it does not solve
The abstract does not establish a specific engineered tool or intervention that fully resolves ER stress in DKD.
The abstract does not define ER stress as a method, assay, or engineered construct.
The review abstract states that the mechanisms linking ER stress to cell death remain unclear and context dependent.
Evidence Snippets
endoplasmic reticulum (ER) stress (ERS) profoundly affects its pathological course
Recent studies have highlighted a significant cellular stress response known as endoplasmic reticulum stress (ERS), which is triggered by hyperglycemia, lipotoxicity, and inflammation, and may serve as a pivotal hub in T2DM pathology.
ER stress, which is an adaptive cellular response to disturbances in protein-folding.
Recent studies have shed light on the pivotal role of prolonged endoplasmic reticulum stress (ERS)-initiated activation of the unfolded protein response (UPR), the ensuing chronic low-grade inflammation, and altered insulin signaling in promoting obesity-compromised cardiovascular system (CVS).
Disturbances in the normal functions of the ER lead to an evolutionarily conserved cell stress response, the unfolded protein response, which is aimed initially at compensating for damage but can eventually trigger cell death if ER dysfunction is severe or prolonged.
Perturbations of ER homeostasis affect protein folding and cause ER stress.
Supporting Sources
Linked Claims
ERS disrupts skeletal muscle homeostasis via UPR pathways including PERK, IRE1α, and ATF6, contributing to insulin resistance and activation of protein degradation systems.
Quoted textsource-backed
This review synthesizes experimental studies to elucidate how ERS disrupts muscle homeostasis via the unfolded protein response (UPR) pathways (PERK, IRE1α, and ATF6) contributing to insulin resistance and activation of protein degradation systems.
Endoplasmic reticulum stress may serve as a pivotal hub in the pathology of type 2 diabetes mellitus affecting skeletal muscle.
Quoted textsource-backed
Recent studies have highlighted a significant cellular stress response known as endoplasmic reticulum stress (ERS), which is triggered by hyperglycemia, lipotoxicity, and inflammation, and may serve as a pivotal hub in T2DM pathology.
ER stress is triggered by imbalance of ER homeostasis and activates the three classical unfolded protein response pathways, including PERK, IRE1α, and ATF6, to restore homeostasis.
In diabetic kidney disease, endoplasmic reticulum stress profoundly affects disease pathology.
ER-stress-induced podocyte injury, renal tubular dysfunction, and extracellular matrix deposition collectively drive progression of diabetic kidney disease.
Sustained ER stress leads to apoptosis and inflammatory responses that accelerate kidney injury.
Intervention strategies targeting ERS may provide prevention and treatment opportunities for T2DM-related muscle disorders.
Quoted textsource-backed
Consequently, intervention strategies targeting ERS may offer new insights and directions for the prevention and treatment of T2DM-related muscle disorders.
The review presents potential clinical interventions for patients with diabetic kidney disease in the context of ER stress.
Prolonged or severe ER stress can activate the unfolded protein response and apoptotic pathways.
Endoplasmic reticulum stress is an adaptive cellular response to disturbances in protein folding.
The source reviews AHR, HIF, SIM, NPAS1-4, and CLOCK with emphasis on their potential role in modulating ER stress.
The review states that prolonged endoplasmic reticulum stress activates unfolded protein response signaling and is implicated in chronic low-grade inflammation and altered insulin signaling that promote obesity-associated cardiovascular dysfunction.
The review presents attenuation of ER-stress-initiated UPR signaling as a promising therapeutic strategy for obesity-associated cardiovascular and metabolic disorders.
ER-initiated cell death pathways have recognized roles in hypoxia, ischemia/reperfusion injury, neurodegeneration, heart disease, and diabetes.
Quoted textsource-backed
Important roles for ER-initiated cell death pathways have been recognized for several diseases, including hypoxia, ischemia/reperfusion injury, neurodegeneration, heart disease, and diabetes.
The mechanisms by which ER stress leads to cell death remain unclear, with multiple candidate participants and uncertain dominant effectors across cellular contexts.
Quoted textsource-backed
The mechanisms by which ER stress leads to cell death remain enigmatic, with multiple potential participants described but little clarity about which specific death effectors dominate in particular cellular contexts.
Disturbances in normal ER function activate the unfolded protein response as an initially compensatory stress response.
Quoted textsource-backed
Disturbances in the normal functions of the ER lead to an evolutionarily conserved cell stress response, the unfolded protein response, which is aimed initially at compensating for damage
If ER dysfunction is severe or prolonged, the unfolded protein response can eventually trigger cell death.
Quoted textsource-backed
but can eventually trigger cell death if ER dysfunction is severe or prolonged
ER stress responses include translational attenuation, upregulation of ER chaperone-related genes, and degradation of unfolded proteins by a quality-control system.
ER stress has been implicated in diabetes, ischemia, and neurodegenerative disorders.
Severe impairment of ER function elicits apoptotic signals.