ArticleEBioMedicine2017
Highly Selective Activation of Heat Shock Protein 70 by Allosteric Regulation Provides an Insight into Efficient Neuroinflammation Inhibition.
Article in EBioMedicine, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 49 citations in OpenAlex.
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- Handelin alleviates cachexia- and aging-induced skeletal muscle atrophy by improving protein homeostasis and inhibiting inflammation.Journal of cachexia, sarcopenia and muscle · 2024Article
- Molecular Chaperones' Potential against Defective Proteostasis of Amyotrophic Lateral Sclerosis.Cells · 2023Review
- Emerging Role of Alarmins in Food Allergy: An Update on Pathophysiological Insights, Potential Use as Disease Biomarkers, and Therapeutic Implications.Journal of clinical medicine · 2023Review
- Macrophage Inactivation by Small Molecule Wedelolactone via Targeting sEH for the Treatment of LPS-Induced Acute Lung Injury.ACS central science · 2023Article
- Direct targeting of sEH with alisol B alleviated the apoptosis, inflammation, and oxidative stress in cisplatin-induced acute kidney injury.International journal of biological sciences · 2023Article
- Effects of Avenanthramide on the Small Intestinal Damage through Hsp70-NF-κB Signaling in an Ovalbumin-Induced Food Allergy Model.International journal of molecular sciences · 2022Article
- Handelin extends lifespan and healthspan of Caenorhabditis elegans by reducing ROS generation and improving motor function.Biogerontology · 2022Article
- Dehydrocostus Lactone Suppresses Dextran Sulfate Sodium-Induced Colitis by Targeting the IKKα/β-NF-κB and Keap1-Nrf2 Signalling Pathways.Frontiers in pharmacology · 2022Article
- HSP70 Ameliorates Septic Acute Kidney Injury via Binding with TRAF6 to Inhibit of Inflammation-Mediated Apoptosis.Journal of inflammation research · 2022Article
- Protocatechuic aldehyde protects cardiomycoytes against ischemic injuryActa pharmaceutica Sinica. B · 2021Article
- Identification of peroxiredoxin 6 as a direct target of withangulatin A by quantitative chemical proteomics in non-small cell lung cancer.Redox biology · 2021Article
- Elucidating direct kinase targets of compound Danshen dropping pills employing archived data and prediction models.Scientific reports · 2021Article
- Stress and immunity in poultry: light management and nanotechnology as effective immune enhancers to fight stress.Cell stress & chaperones · 2021Review
- Small molecule induces mitochondrial fusion for neuroprotection via targeting CK2 without affecting its conventional kinase activity.Signal transduction and targeted therapy · 2021Article
Corrections and comments
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Authors and funding
13 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Heat shock protein 70 (Hsp70) is widely involved in immune disorders, making it as an attractive drug target for inflammation diseases. Nonselective induction of Hsp70 upregulation for inflammation therapy could cause extensive interference in inflammation-unrelated protein functions, potentially resulting in side effects. Nevertheless, direct pharmacological activation of Hsp70 via targeting specific functional amino acid residue may provide an insight into precise Hsp70 function regulation and a more satisfactory treatment effect for inflammation, which has not been extensively focused. Here we show a cysteine residue (Cys306) for selective Hsp70 activation using natural small-molecule handelin. Covalent modification of Cys306 significantly elevates Hsp70 activity and shows more satisfactory anti-neuroinflammation effects. Mechanism study reveals Cys306 modification by handelin induces an allosteric regulation to facilitate adenosine triphosphate hydrolysis capacity of Hsp70, which leads to the effective blockage of subsequent inflammation signaling pathway. Collectively, our study offers some insights into direct pharmacological activation of Hsp70 by specially targeting functional cysteine residue, thus providing a powerful tool for accurately modulating neuroinflammation pathogenesis in human with fewer undesirable adverse effects.
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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.