Purinergic signaling in infectious diseases of the central nervous system

Alves, Vinícius Santos; Leite-Aguiar, Raíssa; Silva, Joyce Pereira da; Coutinho‐Silva, Robson; Savio, Luiz Eduardo Baggio

doi:10.1016/j.bbi.2020.07.026

Cited by 36 publications

(29 citation statements)

References 151 publications

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“…During HCV infection, cells expressing HCV polyprotein have shown enhanced glycolytic function mediated by HIF-1α stabilization, with subsequently lower mitochondrial function, even in the presence of cellular oxygen, leading to increased cellular ATP content [ 39 ]. Increases in ATP levels have been reported in HCMV and herpes simplex-1 virus (HSV-1) infections [ 40 ]. Viral infections also induce ROS that control replication by altering mitochondrial function.…”

Section: Mitochondrial Dynamicsmentioning

confidence: 99%

Role of Mitochondria in Viral Infections

Elesela

Lukacs

2021

Life

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Viral diseases account for an increasing proportion of deaths worldwide. Viruses maneuver host cell machinery in an attempt to subvert the intracellular environment favorable for their replication. The mitochondrial network is highly susceptible to physiological and environmental insults, including viral infections. Viruses affect mitochondrial functions and impact mitochondrial metabolism, and innate immune signaling. Resurgence of host-virus interactions in recent literature emphasizes the key role of mitochondria and host metabolism on viral life processes. Mitochondrial dysfunction leads to damage of mitochondria that generate toxic compounds, importantly mitochondrial DNA, inducing systemic toxicity, leading to damage of multiple organs in the body. Mitochondrial dynamics and mitophagy are essential for the maintenance of mitochondrial quality control and homeostasis. Therefore, metabolic antagonists may be essential to gain a better understanding of viral diseases and develop effective antiviral therapeutics. This review briefly discusses how viruses exploit mitochondrial dynamics for virus proliferation and induce associated diseases.

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Section: Mitochondrial Dynamicsmentioning

confidence: 99%

Role of Mitochondria in Viral Infections

Elesela

Lukacs

2021

Life

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“…Upregulation of CD73 has also been found in glioma (Quezada et al, 2013;Xu et al, 2013), while in a model of multiple sclerosis, upregulation of CD73 and CD39 has been reported in reactive astrocytes and in microglia, respectively (Lavrnja et al, 2015;Jakovljevic et al, 2019). The involvement of ectonucleotidases in the regulation of microglial function, the pathogenesis of infectious diseases in the nervous system and the complex regulation of CD73 at the neurovascular unit during neuroinflammation have been recently reviewed by Nedeljkovic (2019), Alves et al (2020) and Illes et al (2020). Altogether these observations suggest that reduction of CD73 activity, and therefore, adenosine levels, might be a therapeutical tool to decrease neuroinflammation in PD as well as astrogliosis in mesial temporal lobe epilepsy, and likely, to improve cognition in AD and PD.…”

Section: Ectonucleotidasesmentioning

confidence: 99%

Metabolic Aspects of Adenosine Functions in the Brain

et al. 2021

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Adenosine, acting both through G-protein coupled adenosine receptors and intracellularly, plays a complex role in multiple physiological and pathophysiological processes by modulating neuronal plasticity, astrocytic activity, learning and memory, motor function, feeding, control of sleep and aging. Adenosine is involved in stroke, epilepsy and neurodegenerative pathologies. Extracellular concentration of adenosine in the brain is tightly regulated. Adenosine may be generated intracellularly in the central nervous system from degradation of AMP or from the hydrolysis of S-adenosyl homocysteine, and then exit via bi-directional nucleoside transporters, or extracellularly by the metabolism of released nucleotides. Inactivation of extracellular adenosine occurs by transport into neurons or neighboring cells, followed by either phosphorylation to AMP by adenosine kinase or deamination to inosine by adenosine deaminase. Modulation of the nucleoside transporters or of the enzymatic activities involved in the metabolism of adenosine, by affecting the levels of this nucleoside and the activity of adenosine receptors, could have a role in the onset or the development of central nervous system disorders, and can also be target of drugs for their treatment. In this review, we focus on the contribution of 5′-nucleotidases, adenosine kinase, adenosine deaminase, AMP deaminase, AMP-activated protein kinase and nucleoside transporters in epilepsy, cognition, and neurodegenerative diseases with a particular attention on amyotrophic lateral sclerosis and Huntington’s disease. We include several examples of the involvement of components of the adenosine metabolism in learning and of the possible use of modulators of enzymes involved in adenosine metabolism or nucleoside transporters in the amelioration of cognition deficits.

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“…Other inflammatory cells, including monocytes and macrophages, also produce S100A9 in small amounts [ 7 ]. It has been reported that S100A9 can induce immune cell activation via the Toll-like receptor 4 (TLR4) or advanced glycation end products (RAGE) inflammatory signaling pathways [ 8 , 9 ]. Excessive expression of S100A9 has been observed in several infection- and non-infection-induced inflammatory diseases, such as sepsis, myocardial infraction and chronic obstructive pulmonary disease [ 10 – 12 ].…”

Section: Introductionmentioning

confidence: 99%

S100A9 blockade prevents lipopolysaccharide-induced lung injury via suppressing the NLRP3 pathway

Zhao

Chen

et al. 2021

Respir Res

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Background S100 calcium binding protein A9 (S100A9) is a pro-inflammatory alarmin associated with several inflammation-related diseases. However, the role of S100A9 in lung injury in sepsis has not been fully investigated. Therefore, the present study aimed to determine the role of S100A9 in a lipopolysaccharide (LPS)-induced lung injury murine model and its underlying molecular mechanisms. Methods LPS was utilized to induce sepsis and lung injury in C57BL/6 or NOD-like receptor family pyrin domain containing 3 (NLRP3)−/− mice. To investigate the effects of S100A9 blockade, mice were treated with a specific inhibitor of S100A9. Subsequently, lung injury and inflammation were evaluated by histology and enzyme‑linked immunosorbent assay (ELISA), respectively. Furthermore, western blot analysis and RT-qPCR were carried out to investigate the molecular mechanisms underlying the effects of S100A9. Results S100A9 was upregulated in the lung tissues of LPS-treated mice. However, inhibition of S100A9 alleviated LPS-induced lung injury. Additionally, S100A9 blockade also attenuated the inflammatory responses and apoptosis in the lungs of LPS-challenged mice. Furthermore, the increased expression of NLRP3 was also suppressed by S100A9 blockade, while S100A9 blockade had no effect on NLRP3−/− mice. In vitro, S100A9 downregulation mitigated LPS-induced inflammation. Interestingly, these effects were blunted by NLRP3 overexpression. Conclusion The results of the current study suggested that inhibition of S100A9 could protect against LPS-induced lung injury via inhibiting the NLRP3 pathway. Therefore, S100A9 blockade could be considered as a novel therapeutic strategy for lung injury in sepsis.

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Purinergic signaling in infectious diseases of the central nervous system

Cited by 36 publications

References 151 publications

Role of Mitochondria in Viral Infections

Role of Mitochondria in Viral Infections

Metabolic Aspects of Adenosine Functions in the Brain

S100A9 blockade prevents lipopolysaccharide-induced lung injury via suppressing the NLRP3 pathway

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