ArticleCurrent research in pharmacology and drug discovery2022
GSK2606414 attenuates PERK/p-eIF2α/ATF4/CHOP axis and augments mitochondrial function to mitigate high glucose induced neurotoxicity in N2A cells.
Article in Current research in pharmacology and drug discovery, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
26 citing papers in PubMed, 47 citations in OpenAlex.
- Translational dysregulation as a mechanistic driver of cognitive, behavioral, and affective phenotypes in FXS and TSC.Neuroscience and biobehavioral reviews · 2026Review
- The Interaction Between Insulin Resistance and Neuroinflammation in the Brain and Its Impact on Diabetic Encephalopathy.Biology · 2026Review
- Pan-cancer analysis reveals differential PERK expression across tumour types and its potential as a therapeutic target.Discover oncology · 2026Article
- Unfolded Protein Response at the Crossroads: Integrating Endoplasmic Reticulum Stress with Cellular Stress Networks.International journal of molecular sciences · 2026Review
- Phycocyanobilin as a Functional Food-Derived Nutraceutical Candidate for Modulating the RAGE/NOX4 Axis in Neurodegenerative Disorders.Nutrients · 2026Article
- Integrated Bioinformatics and Experimental Validation Reveal Fuzheng Yi'ai Formula Induces Immunogenic Cell Death Via the PERK-eIF2α-ATF4 Pathway for Prostate Cancer Treatment.Biological procedures online · 2026Article
- Renoprotective actions of puerarin and the prospects of kidney-targeted nanodelivery.Frontiers in pharmacology · 2026Review
- Improved bioavailability and anti-nephrotoxicity efficacy of polydatin on cisplatin-induced AKIInternational journal of pharmaceutics: X · 2025Article
- Review
- Dolutegravir induces endoplasmic reticulum stress at the blood-brain barrier.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Free fatty acids may regulate the expression of 11β-hydroxysteroid dehydrogenase type 1 in the liver of high-fat diet golden hamsters through the ERS-CHOP-C/EBPα signaling pathway.Lipids in health and disease · 2025Article
- ER stress sensors at the ER-mitochondrial interface, controlling mitochondrial health in neurodegenerative diseases.Frontiers in neuroscience · 2025Review
- Qizhi Kebitong Formula Ameliorates Sciatic Nerve Injury in Streptozocin-induced Diabetic Mice through PERK/ATF4/CHOP Endoplasmic Reticulum Stress Signaling Pathway.Current pharmaceutical design · 2025Article
- Spring viraemia of carp virus modulates the time-dependent unfolded protein response to facilitate viral replication.Frontiers in immunology · 2025Article
- Relevant Serum Endoplasmic Reticulum Stress Biomarkers in Type 2 Diabetes and Its Complications: A Systematic Review and Meta-Analysis.Antioxidants (Basel, Switzerland) · 2024Review
- Different Types of Cell Death in Diabetic Neuropathy: A Focus on Mechanisms and Therapeutic Strategies.International journal of molecular sciences · 2024Review
- Mammalian integrated stress responses in stressed organelles and their functions.Acta pharmacologica Sinica · 2024Review
- The IRE1α/XBP1 pathway sustains cytokine responses of group 3 innate lymphoid cells in inflammatory bowel disease.The Journal of clinical investigation · 2024Article
- PERK modulation, with GSK2606414, Sephin1 or salubrinal, failed to produce therapeutic benefits in the SOD1G93A mouse model of ALS.PloS one · 2024Article
- Navigating the landscape of the unfolded protein response in CD8Frontiers in immunology · 2024Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Neuronal dysfunction and subsequent apoptosis under high glucose conditions during diabetes contribute majorly to the manifestation of diabetic peripheral neuropathy (DPN). PERK (protein kinase RNA (PKR)-like ER kinase) one among the three canonical arms of unfolded protein response (UPR), is believed to play a crucial role in determining the cell fate during endoplasmic reticulum stress (ERS/ER stress) conditions. We evaluated the role of PERK inhibitor GSK2606414 in high glucose (30 mM) treated neuroblastoma (N2A) cells. High glucose resulted in disruption of ER proteostasis by activation of UPR which is evident through increased (p < 0.001) expression of GRP78, p-PERK, p-eIF2α, ATF-4 and CHOP when compared to normal cells. It is accompanied with enhanced GRP78 localization in Endoplasmic Reticulum (ER) lumen evident from ER labeling Immunofluorescence (IF) staining. PERK activation resulted in altered mitochondrial function evident by increased mitochondrial superoxide production and compromised mitochondrial homeostasis with decrease in Mfn-2 levels. Additionally, ER stress induced neuronal apoptosis was attenuated by GSK2606414 treatment via inhibiting the PERK-eIF2α-ATF4-CHOP axis that not only curtailed the levels of apoptotic proteins like Bax and caspase 3 but also elevated the levels of anti-apoptotic Bcl-2. Collectively, our findings revealed the neuroprotective potential of GSK2606414 against high glucose induced neurotoxicity in N2A cells.
Indexed as
Identifiers
What Socratic holds
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 Socratic graph.