ArticleProceedings of the National Academy of Sciences of the United States of America2008
The PIDDosome mediates delayed death of hippocampal CA1 neurons after transient global cerebral ischemia in rats.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 53 citations in OpenAlex.
- Candidate Mechanisms of Cerebral Ischemia/Hypoxia Tolerance: Insights from Hibernating Rodents.Neurochemical research · 2026Review
- Potential of Polydatin Against Ischemia-Reperfusion Injury: New Insights from Pharmacological-Pathological Mechanism Associations.Drug design, development and therapy · 2025Review
- Article
- An electrophilic fragment screening for the development of small molecules targeting caspase-2.European journal of medicinal chemistry · 2023Article
- Targeting caspase-2 interactions with tau in Alzheimer's disease and related dementias.Translational research : the journal of laboratory and clinical medicine · 2023Review
- PIDD1 in cell cycle control, sterile inflammation and cell death.Biochemical Society transactions · 2022Review
- Supramolecular organizing centers at the interface of inflammation and neurodegeneration.Frontiers in immunology · 2022Review
- Uncovering the PIDDosome and caspase-2 as regulators of organogenesis and cellular differentiation.Cell death and differentiation · 2020Review
- Article
- Rescuing neuronal cell death by RAIDD- and PIDD- derived peptides and its implications for therapeutic intervention in neurodegenerative diseases.Scientific reports · 2016Article
- Cardiac arrest triggers hippocampal neuronal death through autophagic and apoptotic pathways.Scientific reports · 2016Article
- Shenqi fuzheng injection attenuates irradiation-induced brain injury in mice via inhibition of the NF-κB signaling pathway and microglial activation.Acta pharmacologica Sinica · 2015Article
- An Inhibitor of PIDDosome Formation.Molecular cell · 2015Article
- Combined suppression of CASP2 and CASP6 protects retinal ganglion cells from apoptosis and promotes axon regeneration through CNTF-mediated JAK/STAT signalling.Brain : a journal of neurology · 2014Article
- The role of PARL and HtrA2 in striatal neuronal injury after transient global cerebral ischemia.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2013Article
- Inhibition of Sox2 Expression in the Adult Neural Stem Cell Niche In Vivo by Monocationic-based siRNA Delivery.Molecular therapy. Nucleic acids · 2013Article
- Caspase inhibitors: prospective therapies for stroke.The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry · 2013Review
- PI3K/Akt-independent negative regulation of JNK signaling by MKP-7 after cerebral ischemia in rat hippocampus.BMC neuroscience · 2013Article
- Prevention of JNK phosphorylation as a mechanism for rosiglitazone in neuroprotection after transient cerebral ischemia: activation of dual specificity phosphatase.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2013Article
- Review
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
A brief period of global brain ischemia, such as that induced by cardiac arrest or cardiopulmonary bypass surgery, causes cell death in vulnerable hippocampal CA1 pyramidal neurons days after reperfusion. Although numerous factors have been suggested to account for this phenomenon, the mechanisms underlying it are poorly understood. We describe a cell death signal called the PIDDosome, a protein complex of p53-induced protein with a death domain (PIDD), receptor-interacting protein-associated ICH-1/CED-3 homologous protein with a death domain (RAIDD), and procaspase-2. We induced 5 min of transient global cerebral ischemia (tGCI) using bilateral common carotid artery occlusion with hypotension. Western blot analysis showed that expression of twice-cleaved fragment of PIDD (PIDD-CC) increased in the cytosolic fraction of the hippocampal CA1 subregion and preceded procaspase-2 activation after tGCI. Caspase-2 cleaved Bid in brain homogenates. Co-immunoprecipitation and immunofluorescent studies demonstrated that PIDD-CC, RAIDD, and procaspase-2 were co-localized and bound directly, which indicates the formation of the PIDD death domain complex. Furthermore, we tested inhibition of PIDD expression by using small interfering RNA (siRNA) treatment that was initiated 48 h before tGCI. Administration of siRNA against PIDD decreased not only expression of PIDD-CC, but also activation of procaspase-2 and Bid, resulting in a decrease in histological neuronal damage and DNA fragmentation in the hippocampal CA1 subregion after tGCI. These results imply that PIDD plays an important role in procaspase-2 activation and delayed CA1 neuronal death after tGCI. We propose that PIDD is a hypothetical molecular target for therapy against neuronal death after tGCI.
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