scholarly journals Regenerative Effects of Heme Oxygenase Metabolites on Neuroinflammatory Diseases

2018 ◽  
Vol 20 (1) ◽  
pp. 78 ◽  
Author(s):  
Huiju Lee ◽  
Yoon Choi
Keyword(s):  
Endothelial Cells ◽  
Heme Oxygenase ◽  
Neurovascular Unit ◽  
Vascular Diseases ◽  
Cell Types ◽  
Cns Injury ◽  
Perivascular Cells ◽  
Major Barrier ◽  
The Central Nervous System

Heme oxygenase (HO) catabolizes heme to produce HO metabolites, such as carbon monoxide (CO) and bilirubin (BR), which have gained recognition as biological signal transduction effectors. The neurovascular unit refers to a highly evolved network among endothelial cells, pericytes, astrocytes, microglia, neurons, and neural stem cells in the central nervous system (CNS). Proper communication and functional circuitry in these diverse cell types is essential for effective CNS homeostasis. Neuroinflammation is associated with the vascular pathogenesis of many CNS disorders. CNS injury elicits responses from activated glia (e.g., astrocytes, oligodendrocytes, and microglia) and from damaged perivascular cells (e.g., pericytes and endothelial cells). Most brain lesions cause extensive proliferation and growth of existing glial cells around the site of injury, leading to reactions causing glial scarring, which may act as a major barrier to neuronal regrowth in the CNS. In addition, damaged perivascular cells lead to the breakdown of the blood-neural barrier, and an increase in immune activation, activated glia, and neuroinflammation. The present review discusses the regenerative role of HO metabolites, such as CO and BR, in various vascular diseases of the CNS such as stroke, traumatic brain injury, diabetic retinopathy, and Alzheimer’s disease, and the role of several other signaling molecules.

scholarly journals The Role of Astrocytes in the Central Nervous System Focused on BK Channel and Heme Oxygenase Metabolites: A Review

Antioxidants ◽  
2019 ◽  
Vol 8 (5) ◽  
pp. 121 ◽  
Author(s):  
Yonghee Kim ◽  
Jinhong Park ◽  
Yoon Kyung Choi
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Heme Oxygenase ◽  
Molecular Mechanisms ◽  
Nitrosative Stress ◽  
Bk Channel ◽  
Cns Injury ◽  
Antioxidant Agents ◽  
The Central Nervous System

Astrocytes outnumber neurons in the human brain, and they play a key role in numerous functions within the central nervous system (CNS), including glutamate, ion (i.e., Ca2+, K+) and water homeostasis, defense against oxidative/nitrosative stress, energy storage, mitochondria biogenesis, scar formation, tissue repair via angiogenesis and neurogenesis, and synapse modulation. After CNS injury, astrocytes communicate with surrounding neuronal and vascular systems, leading to the clearance of disease-specific protein aggregates, such as β-amyloid, and α-synuclein. The astrocytic big conductance K+ (BK) channel plays a role in these processes. Recently, potential therapeutic agents that target astrocytes have been tested for their potential to repair the brain. In this review, we discuss the role of the BK channel and antioxidant agents such as heme oxygenase metabolites following CNS injury. A better understanding of the cellular and molecular mechanisms of astrocytes’ functions in the healthy and diseased brains will greatly contribute to the development of therapeutic approaches following CNS injury, such as Alzheimer’s disease, Parkinson’s disease, and stroke.

scholarly journals The Microbiota–Gut–Brain Axis and Alzheimer Disease. From Dysbiosis to Neurodegeneration: Focus on the Central Nervous System Glial Cells

2021 ◽  
Vol 10 (11) ◽  
pp. 2358
Author(s):  
Maria Grazia Giovannini ◽  
Daniele Lana ◽  
Chiara Traini ◽  
Maria Giuliana Vannucchi
Keyword(s):  
Alzheimer Disease ◽  
Glial Cells ◽  
Cell Types ◽  
The Past ◽  
The Central Nervous System ◽  
Diseased State ◽  
The Brain ◽  
Alzheimer Disease Pathogenesis ◽  
Brain Homeostasis

The microbiota–gut system can be thought of as a single unit that interacts with the brain via the “two-way” microbiota–gut–brain axis. Through this axis, a constant interplay mediated by the several products originating from the microbiota guarantees the physiological development and shaping of the gut and the brain. In the present review will be described the modalities through which the microbiota and gut control each other, and the main microbiota products conditioning both local and brain homeostasis. Much evidence has accumulated over the past decade in favor of a significant association between dysbiosis, neuroinflammation and neurodegeneration. Presently, the pathogenetic mechanisms triggered by molecules produced by the altered microbiota, also responsible for the onset and evolution of Alzheimer disease, will be described. Our attention will be focused on the role of astrocytes and microglia. Numerous studies have progressively demonstrated how these glial cells are important to ensure an adequate environment for neuronal activity in healthy conditions. Furthermore, it is becoming evident how both cell types can mediate the onset of neuroinflammation and lead to neurodegeneration when subjected to pathological stimuli. Based on this information, the role of the major microbiota products in shifting the activation profiles of astrocytes and microglia from a healthy to a diseased state will be discussed, focusing on Alzheimer disease pathogenesis.

scholarly journals TNF-α-Induced YAP/TAZ Activity Mediates Leukocyte-Endothelial Adhesion by Regulating VCAM1 Expression in Endothelial Cells

2018 ◽  
Vol 19 (11) ◽  
pp. 3428 ◽  
Author(s):  
Hyun-Jung Choi ◽  
Na-Eun Kim ◽  
Byeong Kim ◽  
Miran Seo ◽  
Ji Heo
Keyword(s):  
Endothelial Cells ◽  
Rho Gtpases ◽  
Leukocyte Adhesion ◽  
Hippo Pathway ◽  
Specific Inhibitor ◽  
Vascular Diseases ◽  
Adhesive Properties ◽  
Sprouting Angiogenesis ◽  
Tnf Α

YAP/TAZ, a transcriptional co-activator of Hippo pathway, has emerged as a central player in vessel homeostasis such as sprouting angiogenesis and vascular barrier stabilization, during development. However, the role of YAP/TAZ in pathological angiogenesis remains unclear. Here, we demonstrated that YAP/TAZ is a critical mediator in leukocyte-endothelial adhesion induced by the vascular inflammatory cytokine TNF-α. YAP/TAZ was dephosphorylated, translocated from the cytosol to the nucleus, and activated by TNF-α in endothelial cells. A specific inhibitor of Rho GTPases suppressed the TNF-α-induced dephosphorylation of YAP. Knockdown of YAP/TAZ using siRNA significantly reduced the expression of the leukocyte adhesion molecule VCAM1 induced by TNF-α. The adhesion of monocytes to endothelial cells was also markedly reduced by YAP/TAZ silencing. However, knockdown of YAP/TAZ did not affect TNF-α-induced NF-κB signaling. Overall, these results suggest that YAP/TAZ plays critical roles in regulating TNF-α-induced endothelial cell adhesive properties without affecting the NF-κB pathway, and implicate YAP/TAZ as a potential therapeutic target for treating inflammatory vascular diseases.

scholarly journals Epigenetic regulation of oligodendrocyte myelination in developmental disorders and neurodegenerative diseases

F1000Research ◽  
2020 ◽  
Vol 9 ◽  
pp. 105 ◽  
Author(s):  
Kalen Berry ◽  
Jiajia Wang ◽  
Q. Richard Lu
Keyword(s):  
Neurodegenerative Diseases ◽  
Developmental Disorders ◽  
Cell Types ◽  
Fine Tuning ◽  
Rna Modification ◽  
Cns Injury ◽  
Key Factors ◽  
Chromatin Remodelers ◽  
The Central Nervous System ◽  
Histone Modifying Enzymes

Oligodendrocytes are the critical cell types giving rise to the myelin nerve sheath enabling efficient nerve transmission in the central nervous system (CNS). Oligodendrocyte precursor cells differentiate into mature oligodendrocytes and are maintained throughout life. Deficits in the generation, proliferation, or differentiation of these cells or their maintenance have been linked to neurological disorders ranging from developmental disorders to neurodegenerative diseases and limit repair after CNS injury. Understanding the regulation of these processes is critical for achieving proper myelination during development, preventing disease, or recovering from injury. Many of the key factors underlying these processes are epigenetic regulators that enable the fine tuning or reprogramming of gene expression during development and regeneration in response to changes in the local microenvironment. These include chromatin remodelers, histone-modifying enzymes, covalent modifiers of DNA methylation, and RNA modification–mediated mechanisms. In this review, we will discuss the key components in each of these classes which are responsible for generating and maintaining oligodendrocyte myelination as well as potential targeted approaches to stimulate the regenerative program in developmental disorders and neurodegenerative diseases.

Matrix Stiffening Induces a Pathogenic QKI-miR-7-SRSF1 Signaling Axis in Pulmonary Arterial Endothelial Cells

2021 ◽  
Author(s):  
Chen-Shan Chen Woodcock ◽  
Neha Hafeez ◽  
Adam Handen ◽  
Ying Tang ◽  
Lloyd D Harvey ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Rna Binding ◽  
Vascular Diseases ◽  
Vascular Stiffness ◽  
Artery Stiffness ◽  
Signaling Axis ◽  
Pulmonary Arterial ◽  
Arterial Endothelial Cells ◽  
Splicing Factor 1

Pulmonary arterial hypertension (PAH) refers to a set of heterogeneous vascular diseases defined by elevation of pulmonary arterial pressure (PAP) and pulmonary vascular resistance (PVR), leading to right ventricular (RV) remodeling and often death. Early increases in pulmonary artery stiffness in PAH drive pathogenic alterations of pulmonary arterial endothelial cells (PAECs), leading to vascular remodeling. Dysregulation of microRNAs can drive PAEC dysfunction. However, the role of vascular stiffness in regulating pathogenic microRNAs in PAH is incompletely understood. Here, we demonstrated that extracellular matrix (ECM) stiffening downregulated miR-7 levels in PAECs. The RNA binding protein Quaking (QKI) has been implicated in the biogenesis of miR-7. Correspondingly, we found that ECM stiffness up-regulated QKI, and QKI knockdown led to increased miR-7. Downstream of the QKI-miR-7 axis, the serine and arginine rich splicing factor 1 (SRSF1) was identified as a direct target of miR-7. Correspondingly, SRSF1 was reciprocally up-regulated in PAECs exposed to stiff ECM and was negatively correlated with miR-7. Decreased miR-7 and increased QKI and SRSF1 were observed in lungs from PAH patients and PAH rats exposed to SU5416/hypoxia. Lastly, miR-7 upregulation inhibited human PAEC migration, while forced SRSF1 expression reversed this phenotype, proving that miR-7 depended upon SRSF1 to control migration. In aggregate, these results define the QKI-miR-7-SRSF1 axis as a mechanosensitive mechanism linking pulmonary arterial vascular stiffness to pathogenic endothelial function. These findings emphasize implications relevant to PAH and suggest the potential benefit of developing therapies that target this miRNA-dependent axis in PAH.

A review of bioeffects induced by focused ultrasound combined with microbubbles on the neurovascular unit

2021 ◽  
pp. 0271678X2110461
Author(s):  
Si Chen ◽  
Arash Nazeri ◽  
Hongchae Baek ◽  
Dezhuang Ye ◽  
Yaoheng Yang ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Focused Ultrasound ◽  
Neurovascular Unit ◽  
Cell Types ◽  
Current Treatment ◽  
Clinical Applications ◽  
Brain Diseases ◽  
Great Promise ◽  
Cellular Effects ◽  
Cell Type Specific

Focused ultrasound combined with circulating microbubbles (FUS+MB) can transiently enhance blood-brain barrier (BBB) permeability at targeted brain locations. Its great promise in improving drug delivery to the brain is reflected by a rapidly growing number of clinical trials using FUS+MB to treat various brain diseases. As the clinical applications of FUS+MB continue to expand, it is critical to have a better understanding of the molecular and cellular effects induced by FUS+MB to enhance the efficacy of current treatment and enable the discovery of new therapeutic strategies. Existing studies primarily focus on FUS+MB-induced effects on brain endothelial cells, the major cellular component of BBB. However, bioeffects induced by FUS+MB expand beyond the BBB to cells surrounding blood vessels, including astrocytes, microglia, and neurons. Together these cell types comprise the neurovascular unit (NVU). In this review, we examine cell-type-specific bioeffects of FUS+MB on different NVU components, including enhanced permeability in endothelial cells, activation of astrocytes and microglia, as well as increased intraneuron protein metabolism and neuronal activity. Finally, we discuss knowledge gaps that must be addressed to further advance clinical applications of FUS+MB.

scholarly journals Intranasal Borna Disease Virus (BoDV-1) Infection: Insights into Initial Steps and Potential Contagiosity

2019 ◽  
Vol 20 (6) ◽  
pp. 1318 ◽  
Author(s):  
Alexandra Kupke ◽  
Sabrina Becker ◽  
Konstantin Wewetzer ◽  
Barbara Ahlemeyer ◽  
Markus Eickmann ◽  
...  
Keyword(s):  
Viral Infections ◽  
Cell Types ◽  
Nerve Fibers ◽  
Olfactory Pathway ◽  
Adult Rats ◽  
The Central Nervous System ◽  
Receptor Neurons

Mammalian Bornavirus (BoDV-1) typically causes a fatal neurologic disorder in horses and sheep, and was recently shown to cause fatal encephalitis in humans with and without transplant reception. It has been suggested that BoDV-1 enters the central nervous system (CNS) via the olfactory pathway. However, (I) susceptible cell types that replicate the virus for successful spread, and (II) the role of olfactory ensheathing cells (OECs), remained unclear. To address this, we studied the intranasal infection of adult rats with BoDV-1 in vivo and in vitro, using olfactory mucosal (OM) cell cultures and the cultures of purified OECs. Strikingly, in vitro and in vivo, viral antigen and mRNA were present from four days post infection (dpi) onwards in the olfactory receptor neurons (ORNs), but also in all other cell types of the OM, and constantly in the OECs. In contrast, in vivo, BoDV-1 genomic RNA was only detectable in adult and juvenile ORNs, nerve fibers, and in OECs from 7 dpi on. In vitro, the rate of infection of OECs was significantly higher than that of the OM cells, pointing to a crucial role of OECs for infection via the olfactory pathway. Thus, this study provides important insights into the transmission of neurotropic viral infections with a zoonotic potential.

scholarly journals Endothelial-to-Mesenchymal Transition (EndoMT): Roles in Tumorigenesis, Metastatic Extravasation and Therapy Resistance

2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Valentin Platel ◽  
Sébastien Faure ◽  
Isabelle Corre ◽  
Nicolas Clere
Keyword(s):  
Endothelial Cells ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Cell Types ◽  
Therapy Resistance ◽  
Experimental Conditions ◽  
Potential Implication ◽  
Mesenchymal Transition ◽  
Endothelial To Mesenchymal Transition

Cancer cells evolve in a very complex tumor microenvironment, composed of several cell types, among which the endothelial cells are the major actors of the tumor angiogenesis. Today, these cells are also characterized for their plasticity, as endothelial cells have demonstrated their potential to modify their phenotype to differentiate into mesenchymal cells through the endothelial-to-mesenchymal transition (EndoMT). This cellular plasticity is mediated by various stimuli including transforming growth factor-β (TGF-β) and is modulated dependently of experimental conditions. Recently, emerging evidences have shown that EndoMT is involved in the development and dissemination of cancer and also in cancer cell to escape from therapeutic treatment. In this review, we summarize current updates on EndoMT and its main induction pathways. In addition, we discuss the role of EndoMT in tumorigenesis, metastasis, and its potential implication in cancer therapy resistance.

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