ArticlePLoS biology2014
Modulation of the maladaptive stress response to manage diseases of protein folding.
Article in PLoS biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
61 citing papers in PubMed, 93 citations in OpenAlex.
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- COPII cage assembly factor Sec13 integrates information flow regulating endomembrane function in response to human variation.Scientific reports · 2024Article
- Smooth muscle α-actin missense variant promotes atherosclerosis through modulation of intracellular cholesterol in smooth muscle cells.European heart journal · 2023Article
- Effects of thermal acclimation on the proteome of the planarian Crenobia alpina from an alpine freshwater spring.The Journal of experimental biology · 2022Article
- Spatial covariance analysis reveals the residue-by-residue thermodynamic contribution of variation to the CFTR fold.Communications biology · 2022Article
- Revisiting CFTR Interactions: Old Partners and New Players.International journal of molecular sciences · 2021Review
- Proteome plasticity in response to persistent environmental change.Molecular cell · 2021Article
- The Multifaceted Role of HSF1 in Pathophysiology: Focus on Its Interplay with TG2.International journal of molecular sciences · 2021Review
- Recent advances in understanding the role of proteostasis.Faculty reviews · 2021Review
- Sis1 potentiates the stress response to protein aggregation and elevated temperature.Nature communications · 2020Article
- Proteostasis and Proteotoxicity in the Network Medicine Era.International journal of molecular sciences · 2020Review
- Unbiased Profiling of the Human Proinsulin Biosynthetic Interaction Network Reveals a Role for Peroxiredoxin 4 in Proinsulin Folding.Diabetes · 2020Article
- Alpha-1 Antitrypsin Deficiency-Mediated Liver Toxicity: Why Do Some Patients Do Poorly? What Do We Know So Far?Chronic obstructive pulmonary diseases (Miami, Fla.) · 2020Review
- Correction of Niemann-Pick type C1 trafficking and activity with the histone deacetylase inhibitor valproic acid.The Journal of biological chemistry · 2020Article
- The Effect of Sodium Bicarbonate, a Beneficial Adjuvant Molecule in Cystic Fibrosis, on Bronchial Epithelial Cells Expressing a Wild-Type or Mutant CFTR Channel.International journal of molecular sciences · 2020Article
- Targeting Hsp70 facilitated protein quality control for treatment of polyglutamine diseases.Cellular and molecular life sciences : CMLS · 2020Review
- Unexpected cell type-dependent effects of autophagy on polyglutamine aggregation revealed by natural genetic variation in C. elegans.BMC biology · 2020Article
- Functional Modules of the Proteostasis Network.Cold Spring Harbor perspectives in biology · 2020Review
1 more citing papers are in PubMed but not listed here.
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Authors and funding
13 authors at 6 institutions in 2 countries.
Funding
Abstract
Diseases of protein folding arise because of the inability of an altered peptide sequence to properly engage protein homeostasis components that direct protein folding and function. To identify global principles of misfolding disease pathology we examined the impact of the local folding environment in alpha-1-antitrypsin deficiency (AATD), Niemann-Pick type C1 disease (NPC1), Alzheimer's disease (AD), and cystic fibrosis (CF). Using distinct models, including patient-derived cell lines and primary epithelium, mouse brain tissue, and Caenorhabditis elegans, we found that chronic expression of misfolded proteins not only triggers the sustained activation of the heat shock response (HSR) pathway, but that this sustained activation is maladaptive. In diseased cells, maladaptation alters protein structure-function relationships, impacts protein folding in the cytosol, and further exacerbates the disease state. We show that down-regulation of this maladaptive stress response (MSR), through silencing of HSF1, the master regulator of the HSR, restores cellular protein folding and improves the disease phenotype. We propose that restoration of a more physiological proteostatic environment will strongly impact the management and progression of loss-of-function and gain-of-toxic-function phenotypes common in human disease.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.