ArticleCell stress & chaperones2016
Induction of heat shock proteins in differentiated human neuronal cells following co-application of celastrol and arimoclomol.
Article in Cell stress & chaperones, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 44 citations in OpenAlex.
- Human Hsp70 paralogs display selective J-domain interactions tuning proteostasis under stress.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Carbonic Anhydrase IX Induces Human Osteosarcoma Cell Metastasis by Activating HSPA6 Expression Through the AMPK Signalling Pathway.Journal of cellular and molecular medicine · 2025Article
- Emerging Target Discovery Strategies Drive the Decoding of Therapeutic Power of Natural Products and Further Drug Development: A Case Study of Celastrol.Exploration (Beijing, China) · 2025Review
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- Quantitative Comparison of HSF1 Activators.Molecular biotechnology · 2022Article
- Hsp40 overexpression in pacemaker neurons delays circadian dysfunction in a Drosophila model of Huntington's disease.Disease models & mechanisms · 2022Article
- Heat shock protein Grp78/BiP/HspA5 binds directly to TDP-43 and mitigates toxicity associated with disease pathology.Scientific reports · 2022Article
- Plant-Derived Natural Compounds for the Treatment of Amyotrophic Lateral Sclerosis: An Update.Current neuropharmacology · 2022Review
- Hsp90 Inhibition: A Promising Therapeutic Approach for ARSACS.International journal of molecular sciences · 2021Article
- Heat Shock Protein 70 (HSP70) Induction: Chaperonotherapy for Neuroprotection after Brain Injury.Cells · 2020Review
- Correction of Niemann-Pick type C1 trafficking and activity with the histone deacetylase inhibitor valproic acid.The Journal of biological chemistry · 2020Article
- Article
- Small Heat Shock Proteins, Big Impact on Protein Aggregation in Neurodegenerative Disease.Frontiers in pharmacology · 2019Review
- Defects in Axonal Transport in Inherited Neuropathies.Journal of neuromuscular diseases · 2019Review
- Tau Protein Squired by Molecular Chaperones During Alzheimer's Disease.Journal of molecular neuroscience : MN · 2018Review
- Pharmacological induction of heat shock proteins ameliorates toxicity of mutant PKCγ in spinocerebellar ataxia type 14.The Journal of biological chemistry · 2018Article
- Celastrol treatment protects against acute ischemic stroke-induced brain injury by promoting an IL-33/ST2 axis-mediated microglia/macrophage M2 polarization.Journal of neuroinflammation · 2018Article
- The 70-kDa heat shock protein (Hsp70) as a therapeutic target for stroke.Expert opinion on therapeutic targets · 2018Review
- Knockdown of Heat Shock Proteins HSPA6 (Hsp70B') and HSPA1A (Hsp70-1) Sensitizes Differentiated Human Neuronal Cells to Cellular Stress.Neurochemical research · 2018Article
- Emptying the stores: lysosomal diseases and therapeutic strategies.Nature reviews. Drug discovery · 2018Review
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Few effective therapies exist for the treatment of neurodegenerative diseases that have been characterized as protein misfolding disorders. Upregulation of heat shock proteins (Hsps) mitigates against the accumulation of misfolded, aggregation-prone proteins and synaptic dysfunction, which is recognized as an early event in neurodegenerative diseases. Enhanced induction of a set of Hsps in differentiated human SH-SY5Y neuronal cells was observed following co-application of celastrol and arimoclomol, compared to their individual application. The dosages employed did not affect cell viability or neuronal process morphology. The induced Hsps included the little studied HSPA6 (Hsp70B'), a potentially neuroprotective protein that is present in the human genome but not in rat and mouse and hence is missing in current animal models of neurodegenerative disease. Enhanced induction of HSPA1A (Hsp70-1), DNAJB1 (Hsp40), HO-1 (Hsp32), and HSPB1 (Hsp27) was also observed. Celastrol activates heat shock transcription factor 1 (HSF1), the master regulator of Hsp gene transcription, and also exhibits potent anti-inflammatory and anti-oxidant activities. Arimoclomol is a co-activator that prolongs the binding of activated HSF1 to heat shock elements (HSEs) in the promoter regions of inducible Hsp genes. Elevated Hsp levels peaked at 10 to 12 h for HSPA6, HSPA1A, DNAJB1, and HO-1 and at 24 h for HSPB1. Co-application of celastrol and arimoclomol induced higher Hsp levels compared to heat shock paired with arimoclomol. The co-application strategy of celastrol and arimoclomol targets multiple neurodegenerative disease-associated pathologies including protein misfolding and protein aggregation, inflammatory and oxidative stress, and synaptic dysfunction.
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