Elements toward novel therapeutic targeting of the adrenergic system

Ghanemi, Abdelaziz; Hu, Xintian

doi:10.1016/j.npep.2014.11.003

Cited by 15 publications

(8 citation statements)

References 239 publications

(259 reference statements)

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“…The ADR blocking could reduce the percentages of infected cells that indicated the possibilities of antagonist on severe EV71 infection and implied the importance of ADRs in severe EV71 infection. Moreover, the α- and β-blockers may also influence on mitogen-activated protein kinase (MAPK), NFκB and STAT signaling in the host [ 40 , 41 ]. To further elucidate the mechanism of catecholamines effects, the blockade of catecholamines in EV71-infected animal model will be investigated.…”

Section: Discussionmentioning

confidence: 99%

Norepinephrine and Epinephrine Enhanced the Infectivity of Enterovirus 71

Liao

Wang

et al. 2015

PLoS ONE

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BackgroundEnterovirus 71 (EV71) infections may be associated with neurological complications, including brainstem encephalitis (BE). Severe EV71 BE may be complicated with autonomic nervous system (ANS) dysregulation and/or pulmonary edema (PE). ANS dysregulation is related to the overactivation of the sympathetic nervous system, which results from catecholamine release.ObjectiveThe aims of this study were to explore the effects of catecholamines on severe EV71 infection and to investigate the changes in the percentages of EV71-infected cells, virus titer, and cytokine production on the involvement of catecholamines.Study DesignPlasma levels of norepinephrine (NE) and epinephrine (EP) in EV71-infected patients were measured using an enzyme-linked immunoassay. The expression of adrenergic receptors (ADRs) on RD, A549, SK-N-SH, THP-1, Jurkat and human peripheral blood mononuclear cells (hPBMCs) were detected using flow cytometry. The percentages of EV71-infected cells, virus titer, and cytokine production were investigated after treatment with NE and EP.ResultsThe plasma levels of NE and EP were significantly higher in EV71-infected patients with ANS dysregulation and PE than in controls. Both α1A- and β2-ADRs were expressed on A549, RD, SK-N-SH, HL-60, THP-1, Jurkat cells and hPBMCs. NE treatment elevated the percentages of EV71-infected cells to 62.9% and 22.7% in THP-1 and Jurkat cells, respectively. Via treatment with EP, the percentages of EV71-infected cells were increased to 64.6% and 26.9% in THP-1 and Jurkat cells. The percentage of EV71-infected cells increased upon NE or EP treatment while the α- and β-blockers reduced the percentages of EV71-infected cells with NE or EP treatment. At least two-fold increase in virus titer was observed in EV71-infected A549, SK-N-SH and hPBMCs after treatment with NE or EP. IL-6 production was enhanced in EV71-infected hPBMCs at a concentration of 102 pg/mL NE.ConclusionThe plasma levels of NE and EP elevated in EV71-infected patients with ANS dysregulation and PE. Both NE and EP enhanced the percentages of infected cells and virus titers in EV71 infection in vitro. NE and EP may play a role in the pathogenesis of EV71 BE complicated with ANS dysregulation and PE.

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Section: Discussionmentioning

confidence: 99%

Norepinephrine and Epinephrine Enhanced the Infectivity of Enterovirus 71

Liao

Wang

et al. 2015

PLoS ONE

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“…The main selectivity regarding these systems, although limited to some extent, is conferred by the receptors; two families for DA (D 1 -like including D 1 and D 5 R and D 2 -like including D 2 L, D 2 S, D 3 , D 4 receptor subtypes) (Emilien et al, 1999; Beaulieu and Gainetdinov, 2011), three families also for NA (α 1a,b,d or α 2a−d receptor subtypes, and β receptor subtypes including β 1−3 ) (Andersson, 1980; Ahles and Engelhardt, 2014; Ghanemi and Hu, 2015), four for histamine (H 1−4 ) (Panula et al, 2015) and seven for 5-HT (5-HT 1−7 ) (Barnes and Sharp, 1999; Hoyer et al, 2002). They are mostly G-protein-coupled receptors (GPCR), except for the 5-HT 3 receptor subtypes which are channel receptors.…”

Section: Monoaminergic Systems In the Brainmentioning

confidence: 99%

Monoaminergic and Histaminergic Strategies and Treatments in Brain Diseases

et al. 2016

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The monoaminergic systems are the target of several drugs for the treatment of mood, motor and cognitive disorders as well as neurological conditions. In most cases, advances have occurred through serendipity, except for Parkinson's disease where the pathophysiology led almost immediately to the introduction of dopamine restoring agents. Extensive neuropharmacological studies first showed that the primary target of antipsychotics, antidepressants, and anxiolytic drugs were specific components of the monoaminergic systems. Later, some dramatic side effects associated with older medicines were shown to disappear with new chemical compounds targeting the origin of the therapeutic benefit more specifically. The increased knowledge regarding the function and interaction of the monoaminergic systems in the brain resulting from in vivo neurochemical and neurophysiological studies indicated new monoaminergic targets that could achieve the efficacy of the older medicines with fewer side-effects. Yet, this accumulated knowledge regarding monoamines did not produce valuable strategies for diseases where no monoaminergic drug has been shown to be effective. Here, we emphasize the new therapeutic and monoaminergic-based strategies for the treatment of psychiatric diseases. We will consider three main groups of diseases, based on the evidence of monoamines involvement (schizophrenia, depression, obesity), the identification of monoamines in the diseases processes (Parkinson's disease, addiction) and the prospect of the involvement of monoaminergic mechanisms (epilepsy, Alzheimer's disease, stroke). In most cases, the clinically available monoaminergic drugs induce widespread modifications of amine tone or excitability through neurobiological networks and exemplify the overlap between therapeutic approaches to psychiatric and neurological conditions. More recent developments that have resulted in improved drug specificity and responses will be discussed in this review.

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“…For building an animal model of a neurodegenerative disease such as Alzheimer's disease [13] expressing a specific feature will contribute to study all the NDs that include that specific feature within its pathogenesis. Importantly, this concept is further strengthened by several facts such as the physiology of the brain that constitutes of a network within which the neurotransmitters are in continuous interactions [14] and the common molecular basics [15] related to the G protein coupled receptors [16] that are of a great importance in both neurophysiology [17] and pharmacotherapy [18][19][20]. In addition, other non-degenerative diseases share also similar mechanisms or pathways with some NDs which means that the range of extrapolation of the common features shared by some neurodegenerative disease might also include some non-NDs.…”

Section: Editorialmentioning

confidence: 99%

Unifying the Common Concepts Shared by Neurodegenerative Diseases

Ghanemi¹

2015

JNSK

Self Cite

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Editorialare the results of common underlying pathways or only similar symptoms or phenotypes. These needs collaborations between experts in different fields including the concerned NDs and always study each neurodegenerative disease within the context of the common features shared between more than a neurodegenerative disease and complete the data by cell culture studies results [4], pharmacology [5][6][7][8][9][10] and toxicology [11,12] to reach the final goal which is identify efficient therapies.Such approaches will optimize the efforts aiming to understand the NDs and treat them by reducing the research cost, efforts and time. For building an animal model of a neurodegenerative disease such as Alzheimer's disease [13] expressing a specific feature will contribute to study all the NDs that include that specific feature within its pathogenesis. Importantly, this concept is further strengthened by several facts such as the physiology of the brain that constitutes of a network within which the neurotransmitters are in continuous interactions [14] and the common molecular basics [15] related to the G protein coupled receptors [16] that are of a great importance in both neurophysiology [17] and pharmacotherapy [18][19][20]. In addition, other non-degenerative diseases share also similar mechanisms or pathways with some NDs which means that the range of extrapolation of the common features shared by some neurodegenerative disease might also include some non-NDs.

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Elements toward novel therapeutic targeting of the adrenergic system

Cited by 15 publications

References 239 publications

Norepinephrine and Epinephrine Enhanced the Infectivity of Enterovirus 71

Norepinephrine and Epinephrine Enhanced the Infectivity of Enterovirus 71

Monoaminergic and Histaminergic Strategies and Treatments in Brain Diseases

Unifying the Common Concepts Shared by Neurodegenerative Diseases

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