OCT4B-190 protects against ischemic stroke by modulating GSK-3 β/HDAC6.

OCT4B-190 protects against ischemic stroke by modulating GSK-3β/HDAC6. Exp Neurol. 2019 Apr 11;: Authors: Chen Y, Wu Z, Zhu X, Zhang M, Zang X, Li X, Xu Y Abstract OCT4 is a key regulator in maintaining the pluripotency and self-renewal of embryonic stem cells (ESCs). Human OCT4 gene has three mRNA isoforms, termed OCT4A, OCT4B and OCT4B1. The 190-amino-acid protein isoform (OCT4B-190) is one of the major products of OCT4B mRNA, the biological function of which is still not well defined. Recent evidence suggests that OCT4B-190 may function in the cellular stress response. The glycogen synthase kinase-3β (GSK-3β) and histone deacetylase 6 (HDAC6) are also key stress modulators that play critical roles in the ischemic cascades of stroke. Hence, we here further investigated the effects of OCT4B-190 in the experimental stroke, and explored the underlying roles of GSK-3β and HDAC6. We found that OCT4B-190 overexpression enhanced neuronal viability at 24 h after oxygen-glucose deprivation (OGD) treatment. Moreover, in male C57BL/6 mice subjected to transit middle cerebral artery occlusion (MCAO), OCT4B-190 overexpression reduced infarct volume and improved neurological function after stroke. Notably, we found spatio-temporal alterations of GSK-3β and HDAC6 in the ischemic cortex and striatum, which were affected by adenovirus-mediated OCT4B-190 overexpression. OCT4B-190 demonstrated similar impacts on neuronal cultures in vitro, down...
Source: Experimental Neurology - Category: Neurology Authors: Tags: Exp Neurol Source Type: research

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In this study, we discussed the function and mechanism of LRG1 in acute ischemic stroke from both basic and clinical research points of view. Mice underwent transient middle cerebral artery occlusion (tMCAO) surgery two weeks after LRG1 was overexpressed by the delivery of adeno-associated virus (AAV). For wild-type mice, both the protein and the transcript of LRG1 in the brain tissue were elevated after tMCAO. Meanwhile, the serum levels of LRG1 were decreased after tMCAO. The neuronal injury was shown aggravated in the AAV-LRG1 group (AAV-LRG1 mice with tMCAO) through infarction volume, neurological score, HE, and Nissl ...
Source: Neuroscience - Category: Neuroscience Source Type: research
Publication date: 9 April 2019Source: Cell Reports, Volume 27, Issue 2Author(s): Jianxiong Zeng, Yaoming Wang, Zhifei Luo, Lin-Chun Chang, Ji Seung Yoo, Huan Yan, Younho Choi, Xiaochun Xie, Benjamin E. Deverman, Viviana Gradinaru, Stephanie L. Gupton, Berislav V. Zlokovic, Zhen Zhao, Jae U. JungSummaryExcessive and unresolved neuroinflammation is a key component of the pathological cascade in brain injuries such as ischemic stroke. Here, we report that TRIM9, a brain-specific tripartite motif (TRIM) protein, was highly expressed in the peri-infarct areas shortly after ischemic insults in mice, but expression was decreased ...
Source: Cell Reports - Category: Cytology Source Type: research
Conclusions: The current findings indicate that MST1 participates in SAH-induced BBB disruption and white matter fiber damage via the downstream NF-κB-MMP-9 signaling pathway. Therefore, MST1 antagonists may serve as a novel therapeutic target to prevent early brain injury in SAH patients. PMID: 30018671 [PubMed - in process]
Source: Behavioural Neurology - Category: Neurology Authors: Tags: Behav Neurol Source Type: research
by Michael D. Ehlers, MD, PhD Dr. Ehlers is with Biogen in Cambridge, Massachusetts. Innov Clin Neurosci. 2018;15(3–4):15–16 Funding: No funding was received for the preparation of this article. Disclosures: Dr. Ehlers is an employee and shareholder at Biogen Inc. in Cambridge, Massachusetts. Prominent and expensive failures in Alzheimer’s disease therapies have led to a contagious belief system in some parts of the biopharma industry that neuroscience is just too hard, too risky, and too uncertain. But, might this belief system itself be a residual bias of the past? Close inspection reveals all the signs...
Source: Innovations in Clinical Neuroscience - Category: Neuroscience Authors: Tags: Commentary Current Issue Source Type: research
Adenoviruses-mediated RNA interference targeting cytosolic phospholipase A2α attenuates focal ischemic brain damage in mice. Mol Med Rep. 2018 Feb 15;: Authors: Wu H, Liu H, Zuo F, Zhang L Abstract Cerebral ischemia injury is a clinical, frequently occurring disease, which causes a heavy burden on society and families. It has been demonstrated that cytosolic phospholipase A2α (cPLA2α) is significant in neurological injury caused by ischemic brain injury, and inhibition of cPLA2α may reduce stroke injury. In the present study, the role of cPLA2α was investigated in a m...
Source: Molecular Medicine Reports - Category: Molecular Biology Tags: Mol Med Rep Source Type: research
In conclusion, the present study demonstrated that TIGIT is a prominent negative immune regulator involved in immunosenescence. This novel finding is highly significant, as targeting TIGIT might be an effective strategy to improve the immune response and decrease age-related comorbidities. Delivery of Extracellular Vesicles as a Potential Basis for Therapies https://www.fightaging.org/archives/2018/01/delivery-of-extracellular-vesicles-as-a-potential-basis-for-therapies/ Here I'll point out a readable open access review paper on the potential use of extracellular vesicles as a basis for therapy: harveste...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Conclusions—Using MassTag–polymerase chain reaction, we detected parvovirus B19—a virus known to infect erythrocytes and endothelial cells—in some cases of childhood arterial ischemic stroke. This approach can generate new, testable hypotheses about childhood stroke pathogenesis.
Source: Stroke - Category: Neurology Authors: Tags: Pediatrics, Ischemic Stroke Brief Reports Source Type: research
Angiogenic response is essential for ischemic brain repair. The von Willebrand factor (VWF)–cleaving protease disintegrin and metalloprotease with thrombospondin type I motif, member 13 (ADAMTS13) is required for endothelial tube formation in vitro, but there is currently no in vivo evidence supporting a function of ADAMTS13 in angiogenesis. Here we show that mice deficient in ADAMTS13 exhibited reduced neovascularization, brain capillary perfusion, pericyte and smooth muscle cell coverage on microvessels, expression of the tight junction and basement membrane proteins, and accelerated blood-brain barrier (BBB) break...
Source: Blood - Category: Hematology Authors: Tags: Plenary Papers, Thrombosis and Hemostasis, Vascular Biology Source Type: research
Conclusions -Taken together, our data demonstrate that genetic variation in BAG3 plays an important role in the prevention of ischemic tissue necrosis. These results highlight a pathway that preserves tissue survival and muscle function in the setting of ischemia. PMID: 28442482 [PubMed - as supplied by publisher]
Source: Circulation - Category: Cardiology Authors: Tags: Circulation Source Type: research
CONCLUSIONS Combined VEGF165 and SDF-1 gene therapy represents a potential strategy for improving vascular remodeling and recovery of neural function after cerebral infarction. PMID: 27982773 [PubMed - as supplied by publisher]
Source: Journal of Neurosurgery - Category: Neurosurgery Authors: Tags: J Neurosurg Source Type: research
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