P2X7 receptor in multifaceted cellular signalling and its relevance as a potential therapeutic target in different diseases

Mishra, Abtar; Behura, Assirbad; Kumar, Ashish; Naik, Lincoln; Swain, Ashapoorna; Das, Mousumi; Sarangi, Suman Sudha; Dokania, Puja; Dirisala, Vijaya R.; Bhutia, Sujit K.; Mishra, Amit Kumar; Singh, Ramandeep; Dhiman, Rohan

doi:10.1016/j.ejphar.2021.174235

Cited by 25 publications

(13 citation statements)

References 293 publications

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“…iScience 24, 103478, December 17, 2021 iScience Article ATP and its metabolites have become a critical component of multiple diseases, including HIV and COVID-19 (Abouelkhair, 2020;Alves et al, 2020;de Oliveira et al, 2021;Dos Anjos et al, 2020;Edwards, 2021;Fonteles et al, 2020;Franciosi et al, 2021;Klaver and Thurnher, 2021;Mishra et al, 2021;Pacheco and Faria, 2021;Shan et al, 2020;Simoes and Bagatini, 2021). Our data in long-term HIV-infected individuals indicate that several chronic effects of HIV are correlated with ATP dysfunction and vascular disease, such as cognitive impairment (Velasquez et al, 2020).…”

Section: Ll Open Accessmentioning

confidence: 72%

Pannexin-1 channel opening is critical for COVID-19 pathogenesis

Luu¹,

Valdebenito²,

Scemes³

et al. 2021

iScience

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) rapidly rampaged worldwide, causing a pandemic of coronavirus disease (COVID -19), but the biology of SARS-CoV-2 remains under investigation. We demonstrate that both SARS-CoV-2 spike protein and human coronavirus 229E (hCoV-229E) or its purified S protein, one of the main viruses responsible for the common cold, induce the transient opening of Pannexin-1 (Panx-1) channels in human lung epithelial cells. However, the Panx-1 channel opening induced by SARS-CoV-2 is greater and more prolonged than hCoV-229E/S protein, resulting in an enhanced ATP, PGE 2 , and IL-1b release. Analysis of lung lavages and tissues indicate that Panx-1 mRNA expression is associated with increased ATP, PGE 2 , and IL-1b levels. Panx-1 channel opening induced by SARS-CoV-2 spike protein is angiotensin-converting enzyme 2 (ACE-2), endocytosis, and furin dependent. Overall, we demonstrated that Panx-1 channel is a critical contributor to SARS-CoV-2 infection and should be considered as an alternative therapy.

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Section: Ll Open Accessmentioning

confidence: 72%

Pannexin-1 channel opening is critical for COVID-19 pathogenesis

Luu¹,

Valdebenito²,

Scemes³

et al. 2021

iScience

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“…We further identified downstream signaling pathways following P2X7R activation in the IS-induced migraine model. P2X7R regulates multifaceted cellular signaling pathways including cytokine and chemokine secretion, NLRP3 inflammasome activation, cell death and autophagy [ 42 ]. Among them, the P2X7R-NLRP3 signaling pathway mediating inflammatory response and cell death has been shown to be involved in cognitive impairment in multiple neurological diseases such as AD, VaD and diabetes [ 28 – 30 ].…”

Section: Discussionmentioning

confidence: 99%

P2X7R/NLRP3 signaling pathway-mediated pyroptosis and neuroinflammation contributed to cognitive impairment in a mouse model of migraine

et al. 2022

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Migraine is the second most common form of headache disorder and the second leading cause of disability worldwide. Cognitive symptoms ranked second resulting in migraine-related disability, after pain. P2X7 receptor (P2X7R) was recently shown to be involved in hyperalgesia in migraine. However, the role of P2X7R in migraine-related cognitive impairment is still ill-defined. The aim of this study was to explore the molecular mechanisms underlying migraine-related cognitive impairment and the role of P2X7R in it. Here we used a well-established mouse model of migraine that triggered migraine attacks by application of inflammatory soup (IS) to the dura. Our results showed that repeated dural IS stimulation triggered upregulation of P2X7R, activation of NLRP3 inflammasome, release of proinflammatory cytokines (IL-1β and IL-18) and activation of pyroptotic cell death pathway. Gliosis (microgliosis and astrogliosis), neuronal loss and cognitive impairment also occurred in the IS-induced migraine model. No significant apoptosis or whiter matter damage was observed following IS-induced migraine attacks. These pathological changes occurred mainly in the cerebral cortex and to a less extent in the hippocampus, all of which can be prevented by pretreatment with a specific P2X7R antagonist Brilliant Blue G (BBG). Moreover, BBG can alleviate cognitive impairment following dural IS stimulation. These results identified P2X7R as a key contributor to migraine-related cognitive impairment and may represent a potential therapeutic target for mitigating cognitive impairment in migraine.

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“…Antagonism at P2X7 receptors is assumed to provide multiple benefits ( Mishra et al, 2021 ). Oxidized ATP irreversibly antagonizes P2X7 receptor activation, but lacks selectivity ( Murgia et al, 1993 ; Savio et al, 2018 ; Rotondo et al, 2022 ).…”

Section: Clinically Available Drugsmentioning

confidence: 99%

Neuropathic pain: Mechanisms and therapeutic strategies

Petroianu

Aloum

Adem

2023

Front. Cell Dev. Biol.

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The physiopathology and neurotransmission of pain are of an owe inspiring complexity. Our ability to satisfactorily suppress neuropathic or other forms of chronic pain is limited. The number of pharmacodynamically distinct and clinically available medications is low and the successes achieved modest. Pain Medicine practitioners are confronted with the ethical dichotomy imposed by Hippocrates: On one hand the mandate of primum non nocere, on the other hand, the promise of heavenly joys if successful divinum est opus sedare dolorem. We briefly summarize the concepts associated with nociceptive pain from nociceptive input (afferents from periphery), modulatory output [descending noradrenergic (NE) and serotoninergic (5-HT) fibers] to local control. The local control is comprised of the “inflammatory soup” at the site of pain origin and synaptic relay stations, with an ATP-rich environment promoting inflammation and nociception while an adenosine-rich environment having the opposite effect. Subsequently, we address the transition from nociceptor pain to neuropathic pain (independent of nociceptor activation) and the process of sensitization and pain chronification (transient pain progressing into persistent pain). Having sketched a model of pain perception and processing we attempt to identify the sites and modes of action of clinically available drugs used in chronic pain treatment, focusing on adjuvant (co-analgesic) medication.

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P2X7 receptor in multifaceted cellular signalling and its relevance as a potential therapeutic target in different diseases

Cited by 25 publications

References 293 publications

Pannexin-1 channel opening is critical for COVID-19 pathogenesis

Pannexin-1 channel opening is critical for COVID-19 pathogenesis

P2X7R/NLRP3 signaling pathway-mediated pyroptosis and neuroinflammation contributed to cognitive impairment in a mouse model of migraine

Neuropathic pain: Mechanisms and therapeutic strategies

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