ArticleMolecular therapy : the journal of the American Society of Gene Therapy2017
rAAV8-733-Mediated Gene Transfer of CHIP/Stub-1 Prevents Hippocampal Neuronal Death in Experimental Brain Ischemia.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 20 citations in OpenAlex.
- Mechanistic exploration of ubiquitination-mediated pathways in cerebral ischemic injury.Molecular biology reports · 2024Review
- Clec7a Worsens Long-Term Outcomes after Ischemic Stroke by Aggravating Microglia-Mediated Synapse Elimination.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Ubiquitous regulation of cerebrovascular diseases by ubiquitin-modifying enzymes.Clinical and translational medicine · 2024Review
- CHIP ameliorates neuronal damage in HScientific reports · 2022Article
- Neuronal Death Mechanisms and Therapeutic Strategy in Ischemic Stroke.Neuroscience bulletin · 2022Review
- CHIP ameliorates cerebral ischemia-reperfusion injury by attenuating necroptosis and inflammation.Aging · 2021Article
- Emerging therapeutic targets for cerebral edema.Expert opinion on therapeutic targets · 2021Review
- Extracellular vesicles derived from M2 microglia reduce ischemic brain injury through microRNA-135a-5p/TXNIP/NLRP3 axis.Laboratory investigation; a journal of technical methods and pathology · 2021Article
- CHIP as a therapeutic target for neurological diseases.Cell death & disease · 2020Review
- Article
- The Role of Ubiquitin-Proteasome Pathway and Autophagy-Lysosome Pathway in Cerebral Ischemia.Oxidative medicine and cellular longevity · 2020Review
- Changes in protein function underlie the disease spectrum in patients with CHIP mutations.The Journal of biological chemistry · 2019Article
- Novel adeno‑associated virus‑based genetic vaccines encoding hepatitis C virus E2 glycoprotein elicit humoral immune responses in mice.Molecular medicine reports · 2019Article
- Anisomycin prevents OGD-induced necroptosis by regulating the E3 ligase CHIP.Scientific reports · 2018Article
- Protein Modifications with Ubiquitin as Response to Cerebral Ischemia-Reperfusion Injury.Translational stroke research · 2018Review
- Angiotensin 1-7 Overexpression Mediated by a Capsid-optimized AAV8 Vector Leads to Significant Growth Inhibition of Hepatocellular CarcinomaInternational journal of biological sciences · 2018Article
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Brain ischemia is a major cause of adult disability and death, and it represents a worldwide health problem with significant economic burden for modern society. The identification of the molecular pathways activated after brain ischemia, together with efficient technologies of gene delivery to the CNS, may lead to novel treatments based on gene therapy. Recombinant adeno-associated virus (rAAV) is an effective platform for gene transfer to the CNS. Here, we used a serotype 8 rAAV bearing the Y733F mutation (rAAV8-733) to overexpress co-chaperone E3 ligase CHIP (also known as Stub-1) in rat hippocampal neurons, both in an oxygen and glucose deprivation model in vitro and in a four-vessel occlusion model of ischemia in vivo. We show that CHIP overexpression prevented neuronal degeneration in both cases and led to a decrease of both eIF2α (serine 51) and AKT (serine 473) phosphorylation, as well as reduced amounts of ubiquitinated proteins following hypoxia or ischemia. These data add to current knowledge of ischemia-related signaling in the brain and suggest that gene therapy based on the role of CHIP in proteostasis may provide a new venue for brain ischemia treatment.
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