SUMOtherapeutics for Ischemic Stroke

Karandikar, Paramesh; Gerstl, Jakob V. E.; Kappel, Ari D.; Won, Sae‐Yeon; Dubinski, Daniel; Garcia‐Segura, Monica Emili; Geßler, Florian; See, Alfred P.; Peruzzotti-Jametti, ﻿Luca; Bernstock, Joshua D.

doi:10.3390/ph16050673

Cited by 5 publications

(3 citation statements)

References 108 publications

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“…Those target genes are related to the regulation of apoptosis, protection of neuronal cell death, or regulation of neuronal cell differentiation. SUMO2 is known for its neuroprotective effects [ 83 , 84 , 85 ] while THBS1 regulates axon growth [ 86 ]. CYTB plays a role in the regulation of apoptosis [ 87 ], and NEAT1 is linked to decreased neuronal apoptosis [ 88 , 89 ].…”

Section: Discussionmentioning

confidence: 99%

The Therapeutic Effects of Blueberry-Treated Stem Cell-Derived Extracellular Vesicles in Ischemic Stroke

Jang,

Yu,

Kim

et al. 2024

IJMS

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An ischemic stroke, one of the leading causes of morbidity and mortality, is caused by ischemia and hemorrhage resulting in impeded blood supply to the brain. According to many studies, blueberries have been shown to have a therapeutic effect in a variety of diseases. Therefore, in this study, we investigated whether blueberry-treated mesenchymal stem cell (MSC)-derived extracellular vesicles (B-EVs) have therapeutic effects in in vitro and in vivo stroke models. We isolated the extracellular vesicles using cryo-TEM and characterized the particles and concentrations using NTA. MSC-derived extracellular vesicles (A-EVs) and B-EVs were round with a lipid bilayer structure and a diameter of ~150 nm. In addition, A-EVs and B-EVs were shown to affect angiogenesis, cell cycle, differentiation, DNA repair, inflammation, and neurogenesis following KEGG pathway and GO analyses. We investigated the protective effects of A-EVs and B-EVs against neuronal cell death in oxygen–glucose deprivation (OGD) cells and a middle cerebral artery occlusion (MCAo) animal model. The results showed that the cell viability was increased with EV treatment in HT22 cells. In the animal, the size of the cerebral infarction was decreased, and the behavioral assessment was improved with EV injections. The levels of NeuN and neurofilament heavy chain (NFH)-positive cells were also increased with EV treatment yet decreased in the MCAo group. In addition, the number of apoptotic cells was decreased with EV treatment compared with ischemic animals following TUNEL and Bax/Bcl-2 staining. These data suggested that EVs, especially B-EVs, had a therapeutic effect and could reduce apoptotic cell death after ischemic injury.

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Section: Discussionmentioning

confidence: 99%

The Therapeutic Effects of Blueberry-Treated Stem Cell-Derived Extracellular Vesicles in Ischemic Stroke

Jang,

Yu,

Kim

et al. 2024

IJMS

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“…Treatment for IS patients depends on the time of onset, neurological deficits, and neuroimaging results [ 10 ]. Despite significant advancements in thrombolysis and mechanical thrombectomy over the past decade, IS remains a major contributor to global healthcare burden [ 11 ]. Recombinant human tissue plasminogen activator (rt-PA) is an established intervention for acute IS, with clinical studies demonstrating increasing usage since 2006, highlighting the effectiveness of intravenous thrombolytic therapy [ 12 ].…”

Section: Introductionmentioning

confidence: 99%

Metabolomic discoveries for early diagnosis and traditional Chinese medicine efficacy in ischemic stroke

Wei,

Chen,

Deng

et al. 2024

Biomark Res

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Ischemic stroke (IS), a devastating cerebrovascular accident, presents with high mortality and morbidity. Following IS onset, a cascade of pathological changes, including excitotoxicity, inflammatory damage, and blood-brain barrier disruption, significantly impacts prognosis. However, current clinical practices struggle with early diagnosis and identifying these alterations. Metabolomics, a powerful tool in systems biology, offers a promising avenue for uncovering early diagnostic biomarkers for IS. By analyzing dynamic metabolic profiles, metabolomics can not only aid in identifying early IS biomarkers but also evaluate Traditional Chinese Medicine (TCM) efficacy and explore its mechanisms of action in IS treatment. Animal studies demonstrate that TCM interventions modulate specific metabolite levels, potentially reflecting their therapeutic effects. Identifying relevant metabolites in cerebral ischemia patients holds immense potential for early diagnosis and improved outcomes. This review focuses on recent metabolomic discoveries of potential early diagnostic biomarkers for IS. We explore variations in metabolites observed across different ages, genders, disease severity, and stages. Additionally, the review examines how specific TCM extracts influence IS development through metabolic changes, potentially revealing their mechanisms of action. Finally, we emphasize the importance of integrating metabolomics with other omics approaches for a comprehensive understanding of IS pathophysiology and TCM efficacy, paving the way for precision medicine in IS management.

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“…Presently, over 14,000 SUMO binding domains have been found within the human cell ( Hendriks et al, 2018 ). The span of subsequent potential therapeutic application includes: ischemic stroke ( Karandikar et al, 2023 ), cardiovascular and neurodegenerative disease ( Lee et al, 2016 ; Bernstock et al, 2017a ; Bernstock et al, 2020a ; Chen et al, 2021 ), and oncology ( Seeler and Dejean, 2017 ). Additionally, the druggable characteristics of the SUMO pathway have made it of particular research interest; for example, high throughput screening has allowed for the identification of drugs enhancing SUMO conjugation via inhibition of either microRNAs 182/183 or SUMO-specific protease 2 ( Bernstock et al, 2016 ; Bernstock et al, 2018 ).…”

Section: Introductionmentioning

confidence: 99%

Positioning SUMO as an immunological facilitator of oncolytic viruses for high-grade glioma

Karandikar,

Suh,

Gerstl

et al. 2023

Front. Cell Dev. Biol.

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Oncolytic viral (OV) therapies are promising novel treatment modalities for cancers refractory to conventional treatment, such as glioblastoma, within the central nervous system (CNS). Although OVs have received regulatory approval for use in the CNS, efficacy is hampered by obstacles related to delivery, under-/over-active immune responses, and the “immune-cold” nature of most CNS malignancies. SUMO, the Small Ubiquitin-like Modifier, is a family of proteins that serve as a high-level regulator of a large variety of key physiologic processes including the host immune response. The SUMO pathway has also been implicated in the pathogenesis of both wild-type viruses and CNS malignancies. As such, the intersection of OV biology with the SUMO pathway makes SUMOtherapeutics particularly interesting as adjuvant therapies for the enhancement of OV efficacy alone and in concert with other immunotherapeutic agents. Accordingly, the authors herein provide: 1) an overview of the SUMO pathway and its role in CNS malignancies; 2) describe the current state of CNS-targeted OVs; and 3) describe the interplay between the SUMO pathway and the viral lifecycle and host immune response.

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SUMOtherapeutics for Ischemic Stroke

Cited by 5 publications

References 108 publications

The Therapeutic Effects of Blueberry-Treated Stem Cell-Derived Extracellular Vesicles in Ischemic Stroke

The Therapeutic Effects of Blueberry-Treated Stem Cell-Derived Extracellular Vesicles in Ischemic Stroke

Metabolomic discoveries for early diagnosis and traditional Chinese medicine efficacy in ischemic stroke

Positioning SUMO as an immunological facilitator of oncolytic viruses for high-grade glioma

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