ArticleNature chemical biology2010
Inhibitors of protein disulfide isomerase suppress apoptosis induced by misfolded proteins.
Article in Nature chemical biology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 160 papers.
What it found
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Who cites it
160 citing papers in PubMed, 308 citations in OpenAlex.
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- Amino Acid-Driven Gold Nanochaperone Platforms for Alzheimer's Therapy: A Mechanistic and Design Framework for Protein Misfolding Modulation.Molecular neurobiology · 2026Review
- Targeting the Endoplasmic Reticulum Oxidoreductin-1 Alpha-Protein Disulfide Isomerase Redox Interface as a Therapeutic Strategy in Cancer.Biomedicines · 2026Review
- Noncanonical functions of UGT2B17 promote castration-resistant prostate cancer progression.The Journal of clinical investigation · 2026Article
- Recent Advancements in Pentacyclic and Other Terpenoid Derivatives as Anti-inflammatory Agents.Mini reviews in medicinal chemistry · 2026Review
- Tannic acid inhibits TNF-α signaling by targeting the protein disulfide isomerase and alleviates symptoms in an imiquimod-induced psoriasis mouse model.Cell communication and signaling : CCS · 2025Article
- The leader of the capsid protein fromJournal of virology · 2025Article
- Serum-free cultured meat production by usingiScience · 2025Article
- Characterization of the mechanisms underlying sulfasalazine-induced ferroptotic cell death: role of protein disulfide isomerase-mediated NOS activation and NO accumulation.Acta biochimica et biophysica Sinica · 2025Article
- Optimizing PDIA1 Inhibition as a Strategy to Inhibit NLRP3 Inflammasome Activation and Activity.ACS chemical biology · 2025Article
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- DR5 Disulfide Bonding Functions as a Sensor and Effector of Protein Folding Stress.Molecular cancer research : MCR · 2025Article
- Strong protection by bazedoxifene against chemically-induced ferroptotic neuronal death in vitro and in vivo.Cell communication and signaling : CCS · 2025Article
- Delineating cysteine-reactive compound modulation of cellular proteostasis processes.Nature chemical biology · 2025Article
- A novel neuroprotective mechanism of selegiline by suppressing the pro-apoptotic activity of protein disulfide isomerase.Molecular biomedicine · 2025Article
- Broad-spectrum inflammasome inhibition by thiomuscimol.Cell death discovery · 2024Article
- Mechanism of RSL3-induced ferroptotic cell death in HT22 cells: crucial role of protein disulfide isomerase.Acta biochimica et biophysica Sinica · 2024Article
- Protein disulfide isomerase plays a crucial role in mediating chemically-induced, glutathione depletion-associated hepatocyte injury in vitro and in vivo.Cell communication and signaling : CCS · 2024Article
- Endoplasmic reticulum stress-a key guardian in cancer.Cell death discovery · 2024Review
100 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
Abstract
A hallmark of many neurodegenerative diseases is accumulation of misfolded proteins within neurons, leading to cellular dysfunction and cell death. Although several mechanisms have been proposed to link protein misfolding to cellular toxicity, the connection remains enigmatic. Here, we report a cell death pathway involving protein disulfide isomerase (PDI), a protein chaperone that catalyzes isomerization, reduction and oxidation of disulfides. Through a small molecule screening approach, we discovered five structurally distinct compounds that prevent apoptosis induced by mutant huntingtin protein. Using modified Huisgen cycloaddition chemistry, we then identified PDI as the molecular target of these small molecules. Expression of polyglutamine-expanded huntingtin exon 1 in PC12 cells caused PDI to accumulate at mitochondrial-associated ER membranes and trigger apoptotic cell death via mitochondrial outer-membrane permeabilization. Inhibiting PDI in rat brain cells suppressed the toxicity of mutant huntingtin exon 1 and Aβ peptides processed from the amyloid precursor protein. This pro-apoptotic function of PDI represents a new mechanism linking protein misfolding and apoptotic cell death.
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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.