ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2008
Hsp27 protects against ischemic brain injury via attenuation of a novel stress-response cascade upstream of mitochondrial cell death signaling.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 86 papers, 1 of them a synthesis that pooled it.
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Who cites it
86 citing papers in PubMed, 1 synthesis or guideline pooled it, 139 citations in OpenAlex.
- Method parameters' impact on mortality and variability in mouse stroke experiments: a meta-analysis.Scientific reports · 2016Pooled it
- Chronic Heat Stress Is Associated with Brain Injury, Blood-Brain Barrier Impairment, and Neuroinflammatory Gene Expression in Broilers.Veterinary sciences · 2026Article
- circLOC375190 promotes autophagy through modulation of the mTORC1/TFEB axis in acute ischemic stroke-induced neurological injury.Clinics (Sao Paulo, Brazil) · 2025Article
- Circular RNA PTP4A2 regulates microglial polarization through STAT3 to promote neuroinflammation in ischemic stroke.CNS neuroscience & therapeutics · 2024Article
- Chaperones vs. oxidative stress in the pathobiology of ischemic stroke.Frontiers in molecular neuroscience · 2024Review
- Review
- A Novel Needle Mouse Model of Vascular Cognitive Impairment and Dementia.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- Protein kinase D2 confers neuroprotection by promoting AKT and CREB activation in ischemic stroke.Neurobiology of disease · 2023Article
- Crossroad between the Heat Shock Protein and Inflammation Pathway in Acquiring Drug Resistance: A Possible Target for Future Cancer Therapeutics.Biomedicines · 2023Review
- The Role of NMDA Receptor Partial Antagonist, Carbamathione, as a Therapeutic Agent for Transient Global Ischemia.Biomedicines · 2023Article
- Feasibility of detecting snake envenomation biomarkers from dried blood spots.Analytical science advances · 2023Article
- Conditional knockout of ASK1 in microglia/macrophages attenuates epileptic seizures and long-term neurobehavioural comorbidities by modulating the inflammatory responses of microglia/macrophages.Journal of neuroinflammation · 2022Article
- Interleukin 13 promotes long-term recovery after ischemic stroke by inhibiting the activation of STAT3.Journal of neuroinflammation · 2022Article
- Impact of Heat Shock Proteins in Neurodegeneration: Possible Therapeutical Targets.Annals of neurosciences · 2022Review
- Down-regulation of circular RNA CDC14A peripherally ameliorates brain injury in acute phase of ischemic stroke.Journal of neuroinflammation · 2021Article
- High-salt diet downregulates TREM2 expression and blunts efferocytosis of macrophages after acute ischemic stroke.Journal of neuroinflammation · 2021Article
- Multifaceted Functions of Protein Kinase D in Pathological Processes and Human Diseases.Biomolecules · 2021Review
- Geranylgeranylacetone attenuates cerebral ischemia-reperfusion injury in rats through the augmentation of HSP 27 phosphorylation: a preliminary study.BMC neuroscience · 2021Article
- Sickle cell disease mice have cerebral oxidative stress and vascular and white matter abnormalities.Blood cells, molecules & diseases · 2021Article
- Temporal and Spatial Dynamics of Inflammasome Activation After Ischemic Stroke.Frontiers in neurology · 2021Article
26 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
Abstract
Heat shock protein 27 (Hsp27), a recently discovered member of the heat shock protein family, is markedly induced in the brain after cerebral ischemia and other injury states. In non-neuronal systems, Hsp27 has potent cell death-suppressing functions. However, the mechanism of Hsp27-mediated neuroprotection has not yet been elucidated. Using transgenic and viral overexpression of Hsp27, we investigated the molecular mechanism by which Hsp27 exerts its neuroprotective effect. Overexpression of Hsp27 conferred long-lasting tissue preservation and neurobehavioral recovery, as measured by infarct volume, sensorimotor function, and cognitive tasks up to 3 weeks following focal cerebral ischemia. Examination of signaling pathways critical to neuronal death demonstrated that Hsp27 overexpression led to the suppression of the MKK4/JNK kinase cascade. While Hsp27 overexpression did not suppress activation of an upstream regulatory kinase of the MKK/JNK cascade, ASK1, Hsp27 effectively inhibited ASK1 activity via a physical association through its N-terminal domain and the kinase domain of ASK1. The N-terminal region of Hsp27 was required for neuroprotective function against in vitro ischemia. Moreover, knockdown of ASK1 or inhibition of the ASK1/MKK4 cascade effectively inhibited cell death following neuronal ischemia. This underscores the importance of this kinase cascade in the progression of ischemic neuronal death. Inhibition of PI3K had no effect on Hsp27-mediated neuroprotection, suggesting that Hsp27 does not promote cell survival via activation of PI3K/Akt. Based on these findings, we conclude that overexpression of Hsp27 confers long-lasting neuroprotection against ischemic brain injury via a previously unexplored association and inhibition of ASK1 kinase signaling.
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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.