scholarly journals Therapeutic potential of targeting G protein-gated inwardly rectifying potassium (GIRK) channels in the central nervous system

2021 ◽  
Vol 223 ◽  
pp. 107808
Author(s):  
Danko Jeremic ◽  
Irene Sanchez-Rodriguez ◽  
Lydia Jimenez-Diaz ◽  
Juan D. Navarro-Lopez
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
G Protein ◽  
Therapeutic Potential ◽  
Girk Channels ◽  
The Central Nervous System ◽  
Inwardly Rectifying

RAS in the Central Nervous System: Potential Role in Neuropsychiatric Disorders

2018 ◽  
Vol 25 (28) ◽  
pp. 3333-3352 ◽  
Author(s):  
Natalia Pessoa Rocha ◽  
Ana Cristina Simoes e Silva ◽  
Thiago Ruiz Rodrigues Prestes ◽  
Victor Feracin ◽  
Caroline Amaral Machado ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Central Nervous System ◽  
Nervous System ◽  
Therapeutic Potential ◽  
Neuropsychiatric Disorders ◽  
Extensive Literature ◽  
Ang Ii ◽  
Mas Receptor ◽  
The Central Nervous System ◽  
The Brain

Background: The Renin-Angiotensin System (RAS) is a key regulator of cardiovascular and renal homeostasis, but also plays important roles in mediating physiological functions in the central nervous system (CNS). The effects of the RAS were classically described as mediated by angiotensin (Ang) II via angiotensin type 1 (AT1) receptors. However, another arm of the RAS formed by the angiotensin converting enzyme 2 (ACE2), Ang-(1-7) and the Mas receptor has been a matter of investigation due to its important physiological roles, usually counterbalancing the classical effects exerted by Ang II. Objective: We aim to provide an overview of effects elicited by the RAS, especially Ang-(1-7), in the brain. We also aim to discuss the therapeutic potential for neuropsychiatric disorders for the modulation of RAS. Method: We carried out an extensive literature search in PubMed central. Results: Within the brain, Ang-(1-7) contributes to the regulation of blood pressure by acting at regions that control cardiovascular functions. In contrast with Ang II, Ang-(1-7) improves baroreflex sensitivity and plays an inhibitory role in hypothalamic noradrenergic neurotransmission. Ang-(1-7) not only exerts effects related to blood pressure regulation, but also acts as a neuroprotective component of the RAS, for instance, by reducing cerebral infarct size, inflammation, oxidative stress and neuronal apoptosis. Conclusion: Pre-clinical evidence supports a relevant role for ACE2/Ang-(1-7)/Mas receptor axis in several neuropsychiatric conditions, including stress-related and mood disorders, cerebrovascular ischemic and hemorrhagic lesions and neurodegenerative diseases. However, very few data are available regarding the ACE2/Ang-(1-7)/Mas receptor axis in human CNS.

Role of the glucose-dependent insulinotropic polypeptide and its receptor in the central nervous system: therapeutic potential in neurological diseases

2010 ◽  
Vol 21 (5-6) ◽  
pp. 394-408 ◽  
Author(s):  
Cláudia P. Figueiredo ◽  
Fabrício A. Pamplona ◽  
Tânia L. Mazzuco ◽  
Aderbal S. Aguiar ◽  
Roger Walz ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Therapeutic Potential ◽  
Neurological Diseases ◽  
The Central Nervous System

scholarly journals Dexamethasone promotes IL-4-induced alternative activation at PPARγ point, instead of upstream STAT6 in BV2 microglial cells

2020 ◽  
Author(s):  
Zongfeng Chen ◽  
Liang Zhang ◽  
Xin Xue ◽  
Peng Liu ◽  
Xiang Yin ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Therapeutic Potential ◽  
Polarization State ◽  
Microglial Cells ◽  
Alternative Activation ◽  
Peroxisome Proliferator ◽  
Activation Markers ◽  
Arginase 1 ◽  
The Central Nervous System

Abstract Background Microglia are innate immune effector cells in the central nervous system and play an extremely important role in the physiological processes of the central nervous system. When microglia are activated, there are two polarization states, M1 and M2 phenotype. Dexamethasone is a glucocorticoid widely used in clinical practice, which pharmacological effects are mainly anti-inflammatory, anti-toxic. However, whether Dexamethasone affects polarization state of microglia is unknown. In this study, we investigate the effect of Dexamethasone on IL-4-induced alternative activation in murine BV-2 microglial cells. Methods BV-2 cells were incubated with Dexamethasone alone, IL-4 alone, or the combination of Dexamethasone and IL-4. Western blot and immunofluorescence were performed to detect protein levels of alternative activation markers arginase 1 (Arg1), found in inflammatory zone 1 (FIZZ1). Moreover, we investigated the effects of Dexamethasone on IL-4 induced activation of signal transducer and activators of transcription 6 (STAT6) and peroxisome proliferator-activated receptor-gamma (PPARγ). Results Dexamethasone promoted IL-4 induced microglia alternative activation by increasing the expression of Arg1 and FIZZ1. Dexamethasone also enhanced the expression of PPARγ. These effects were reversed by RU486 (a Dexamethasone antagonist). Further, the effects of Dexamethasone and IL-4 on Arg1 and FIZZ1 were blocked by the application of GW9662 (a PPARγ antagonist). Conclusions Our studies confirm that Dexamethasone promotes IL-4 induced alternative activation via STAT6/PPARγ signaling pathways in microglia. At the same time, it was confirmed that Dexamethasone acts on PPARγ instead of STAT6. These findings support that Dexamethasone has a therapeutic potential for neuroinflammatory diseases via alternative activation.

scholarly journals Activation and Regulation of Cellular Inflammasomes: Gaps in Our Knowledge for Central Nervous System Injury

2014 ◽  
Vol 34 (3) ◽  
pp. 369-375 ◽  
Author(s):  
Juan Pablo de Rivero Vaccari ◽  
W Dalton Dietrich ◽  
Robert W Keane
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Therapeutic Potential ◽  
Interleukin 1 ◽  
Cns Injury ◽  
Cord Injury ◽  
Cns Trauma ◽  
The Central Nervous System ◽  
Brain And Spinal Cord

The inflammasome is an intracellular multiprotein complex involved in the activation of caspase-1 and the processing of the proinflammatory cytokines interleukin-1 β (IL-1 β) and IL-18. The inflammasome in the central nervous system (CNS) is involved in the generation of an innate immune inflammatory response through IL-1 cytokine release and in cell death through the process of pyroptosis. In this review, we consider the different types of inflammasomes (NLRP1, NLRP2, NLRP3, and AIM2) that have been described in CNS cells, namely neurons, astrocytes, and microglia. Importantly, we focus on the role of the inflammasome after brain and spinal cord injury and cover the potential activators of the inflammasome after CNS injury such as adenosine triphosphate and DNA, and the therapeutic potential of targeting the inflammasome to improve outcomes after CNS trauma.

FTY720 on the way from the base camp to the summit of the mountain: relevance for remyelination

2012 ◽  
Vol 18 (3) ◽  
pp. 258-263 ◽  
Author(s):  
M Kipp ◽  
S Amor
Keyword(s):  
Multiple Sclerosis ◽  
Central Nervous System ◽  
Nervous System ◽  
Therapeutic Potential ◽  
Oral Disease ◽  
S1p Receptors ◽  
Receptor Modulator ◽  
Sphingosine 1 Phosphate ◽  
The Central Nervous System

FTY720 (fingolimod; Gilenya®), a sphingosine 1-phosphate (S1P) receptor modulator, is the first oral disease-modifying therapy to be approved for the treatment of relapsing–remitting multiple sclerosis. FTY720 is rapidly converted in vivo to the active S-fingolimod-phosphate, which binds to S1P receptors. This action inhibits egress of lymphocytes from the lymph nodes, preventing entry into the blood and thus infiltration into the central nervous system. More recent studies, however, convincingly show that FTY720 crosses the blood–brain barrier, where it is thought to act on S1P receptors on cells within the central nervous system, such as astrocytes, oligodendrocytes or microglia. Here we discuss the evidence showing that FTY720 also plays a role in remyelination and repair within the brain. While the mechanisms of action still require firm elucidation, it is clear that FTY720 could also be reparative, extending its therapeutic potential for multiple sclerosis.

scholarly journals G-protein involvement in central-nervous-system muscarinic-receptor-coupled polyphosphoinositide hydrolysis

1988 ◽  
Vol 256 (3) ◽  
pp. 995-999 ◽  
Author(s):  
A S Chiu ◽  
P P Li ◽  
J J Warsh
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
G Protein ◽  
Protein S ◽  
Muscarinic Agonist ◽  
Gtp Binding ◽  
Inositol 1,4,5 Trisphosphate ◽  
The Central Nervous System ◽  
New Evidence

Potentiation of muscarinic-agonist-stimulated polyphosphoinositide (PPI) hydrolysis was demonstrated in a rat cerebral-cortical membrane preparation prelabelled with myo-[3H]inositol. Accumulation of myo-[3H]inositol 1,4-bisphosphate ([3H]IP2) was used to assess brain [3H]phosphatidylinositol 4,5-bisphosphate hydrolysis as its immediate metabolite, myo-[3H]inositol 1,4,5-trisphosphate, was rapidly hydrolysed to [3H]IP2. Inclusion of ATP (100 microM) and Mg2+ (5 mM) in the assay medium was necessary to demonstrate the effect of GTP analogues on carbachol-stimulated brain [3H]PPI turnover. Carbachol (100 microM) induced only a small increment in [3H]IP2 accumulation (142% of control) in 1 min. However, its effect was markedly enhanced, to 800% and 300% of control, by 100 microM-guanosine 5′-[gamma-thio]triphosphate (GTP[S]) and guanosine 5′-[beta gamma-imido]triphosphate (p[NH]ppG) respectively. GTP[S] and p[NH]ppG also stimulated [3H]IP2 accumulation by over 500% and 200% of control, respectively. The GTP-analogue-potentiated carbachol effect was antagonized by 10 microM-atropine, whereas the GTP-analogue stimulation was unaffected. This report confirms the involvement of a G (GTP-binding) protein(s) in brain PPI metabolism and provides new evidence for the role of G protein(s) in the coupling of stimulated muscarinic receptors to PPI hydrolysis in the central nervous system.

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