ArticleMolecular neurodegeneration2015
Intrathecal heat shock protein 60 mediates neurodegeneration and demyelination in the CNS through a TLR4- and MyD88-dependent pathway.
Article in Molecular neurodegeneration, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 65 citations in OpenAlex.
- HSP60 Mediates NLRP3 Inflammasome-Dependent Microglial Pyroptosis Via the TLR4/MyD88/NF-κB Signaling Axis After Subarachnoid Hemorrhage.Inflammation · 2026Article
- Review
- Cannabinoids as Multitarget Drugs for the Treatment of Autoimmunity in Glaucoma.ACS pharmacology & translational science · 2025Review
- Microglia and Astrocytes in Alzheimer's Disease: Significance and Summary of Recent Advances.Aging and disease · 2024Review
- The effect of Urtica dioica extract on oxidative stress, heat shock proteins, and brain histopathology in multiple sclerosis model.Physiological reports · 2022Article
- Review
- Toward the Decipherment of Molecular Interactions in the Diabetic Brain.Biomedicines · 2022Review
- Impact of Heat Shock Proteins in Neurodegeneration: Possible Therapeutical Targets.Annals of neurosciences · 2022Review
- MicroRNA-100-5p and microRNA-298-5p released from apoptotic cortical neurons are endogenous Toll-like receptor 7/8 ligands that contribute to neurodegeneration.Molecular neurodegeneration · 2021Article
- Neuroinflammation in Primary Open-Angle Glaucoma.Journal of clinical medicine · 2020Review
- Abnormal Cannabidiol Affects Production of Pro-Inflammatory Mediators and Astrocyte Wound Closure in Primary Astrocytic-Microglial Cocultures.Molecules (Basel, Switzerland) · 2020Article
- Role of Mitochondrial Stress Protein HSP60 in Diabetes-Induced Neuroinflammation.Mediators of inflammation · 2020Review
- Adaptive Immunity: New Aspects of Pathogenesis Underlying Neurodegeneration in Glaucoma and Optic Neuropathy.Frontiers in immunology · 2020Review
- Lack of TLR4 modifies the miRNAs profile and attenuates inflammatory signaling pathways.PloS one · 2020Article
- Mapping Spatiotemporal Microproteomics Landscape in Experimental Model of Traumatic Brain Injury Unveils a link to Parkinson's Disease.Molecular & cellular proteomics : MCP · 2019Article
- Identification of proteins differentially expressed by glutamate treatment in cerebral cortex of neonatal rats.Laboratory animal research · 2019Article
- Heat-Shock Proteins in Neuroinflammation.Frontiers in pharmacology · 2019Review
- Effect of Inflammatory Mediators Lipopolysaccharide and Lipoteichoic Acid on Iron Metabolism of Differentiated SH-SY5Y Cells Alters in the Presence of BV-2 Microglia.International journal of molecular sciences · 2018Article
- Mitochondrial Chaperones in the Brain: Safeguarding Brain Health and Metabolism?Frontiers in endocrinology · 2018Article
- Neuroprotective effect of heat shock protein 60 on matrine-suppressed microglial activation.Experimental and therapeutic medicine · 2017Article
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundToll-like receptors (TLR) constitute a highly conserved class of receptors through which the innate immune system responds to both pathogen- and host-derived factors. Although TLRs are involved in a wide range of central nervous system (CNS) disorders including neurodegenerative diseases, the molecular events leading from CNS injury to activation of these innate immune receptors remain elusive. The stress protein heat shock protein 60 (HSP60) released from injured cells is considered an endogenous danger signal of the immune system. In this context, the main objective of the present study was to investigate the impact of extracellular HSP60 on the brain in vivo.
resultsWe show here that HSP60 injected intrathecally causes neuronal and oligodendrocyte injury in the CNS in vivo through TLR4-dependent signaling. Intrathecal HSP60 results in neuronal cell death, axonal injury, loss of oligodendrocytes, and demyelination in the cerebral cortex of wild-type mice. In contrast both mice lacking TLR4 and the TLR adaptor molecule MyD88 are protected against deleterious effects induced by HSP60. In contrast to the exogenous TLR4 ligand, lipopolysaccharide, intrathecal HSP60 does not induce such a considerable inflammatory response in the brain. In the CNS, endogenous HSP60 is predominantly expressed in neurons and released during brain injury, since the cerebrospinal fluid (CSF) from animals of a mouse stroke model contains elevated levels of this stress protein compared to the CSF of sham-operated mice.
conclusionsOur data show a direct toxic effect of HSP60 towards neurons and oligodendrocytes in the CNS. The fact that these harmful effects involve TLR4 and MyD88 confirms a molecular pathway mediated by the release of endogenous TLR ligands from injured CNS cells common to many forms of brain diseases that bi-directionally links CNS injury and activation of the innate immune system to neurodegeneration and demyelination in vivo.
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