Emerging roles of the P2X7 receptor in cancer pain

Wu, Ping; Wang, Yin; Liu, Yan; Zhou, Guohua; Wu, Xiaoqi; Wen, Qingping

doi:10.1007/s11302-022-09902-1

Cited by 7 publications

(4 citation statements)

References 85 publications

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“…Likewise, the activation of NLRP3 and induction of A1 astrocytes was also demonstrated in primary cultures of murine astrocytes stimulated with lipopolysaccharide (LPS) [ 23 ]. NLRP3 can also be activated by P2X purinoceptor 7 (P2X7R) stimulation, which is expressed in microglia and astrocytes [ 24 ]. P2X7R stimulation is known to induce the release of bioactive molecules, including pro-inflammatory cytokines, chemokines, proteases, reactive oxygen species (ROS), nitrogen molecules, and excitotoxic glutamate, all capable of causing neurodegeneration [ 24 ].…”

Section: Intracellular Signaling Pathways Regulating Astrocytic Pheno...mentioning

confidence: 99%

“…NLRP3 can also be activated by P2X purinoceptor 7 (P2X7R) stimulation, which is expressed in microglia and astrocytes [ 24 ]. P2X7R stimulation is known to induce the release of bioactive molecules, including pro-inflammatory cytokines, chemokines, proteases, reactive oxygen species (ROS), nitrogen molecules, and excitotoxic glutamate, all capable of causing neurodegeneration [ 24 ]. P2X7R is also involved in the ATP-induced membrane pores that allow an excessive influx of Ca 2+ and depletion of intracellular ions and metabolites, ultimately leading to the lysis of antigen-presenting cells as microglia ( Figure 1 ).…”

Section: Intracellular Signaling Pathways Regulating Astrocytic Pheno...mentioning

confidence: 99%

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Neurodegenerative Diseases: Unraveling the Heterogeneity of Astrocytes

Santiago-Balmaseda,

Aguirre-Orozco,

Valenzuela-Arzeta

et al. 2024

Cells

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The astrocyte population, around 50% of human brain cells, plays a crucial role in maintaining the overall health and functionality of the central nervous system (CNS). Astrocytes are vital in orchestrating neuronal development by releasing synaptogenic molecules and eliminating excessive synapses. They also modulate neuronal excitability and contribute to CNS homeostasis, promoting neuronal survival by clearance of neurotransmitters, transporting metabolites, and secreting trophic factors. Astrocytes are highly heterogeneous and respond to CNS injuries and diseases through a process known as reactive astrogliosis, which can contribute to both inflammation and its resolution. Recent evidence has revealed remarkable alterations in astrocyte transcriptomes in response to several diseases, identifying at least two distinct phenotypes called A1 or neurotoxic and A2 or neuroprotective astrocytes. However, due to the vast heterogeneity of these cells, it is limited to classify them into only two phenotypes. This review explores the various physiological and pathophysiological roles, potential markers, and pathways that might be activated in different astrocytic phenotypes. Furthermore, we discuss the astrocyte heterogeneity in the main neurodegenerative diseases and identify potential therapeutic strategies. Understanding the underlying mechanisms in the differentiation and imbalance of the astrocytic population will allow the identification of specific biomarkers and timely therapeutic approaches in various neurodegenerative diseases.

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Section: Intracellular Signaling Pathways Regulating Astrocytic Pheno...mentioning

confidence: 99%

Section: Intracellular Signaling Pathways Regulating Astrocytic Pheno...mentioning

confidence: 99%

Neurodegenerative Diseases: Unraveling the Heterogeneity of Astrocytes

Santiago-Balmaseda,

Aguirre-Orozco,

Valenzuela-Arzeta

et al. 2024

Cells

View full text Add to dashboard Cite

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“…The activation of the central downstream emmetropic system by P2X7R may contribute to the exacerbation of cancer pain and comorbid depression. Therefore, targeting P2X7R may be a valuable therapeutic approach for managing cancer pain and secondary depression 224 …”

Section: Immunotherapy Against P2x7rmentioning

confidence: 99%

“…Therefore, targeting P2X7R may be a valuable therapeutic approach for managing cancer pain and secondary depression. 224 …”

Section: Immunotherapy Against P2x7rmentioning

confidence: 99%

Purine and purinergic receptors in health and disease

Ai,

Wang,

Liu

et al. 2023

MedComm

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Purines and purinergic receptors are widely distributed throughout the human body. Purine molecules within cells play crucial roles in regulating energy metabolism and other cellular processes, while extracellular purines transmit signals through specific purinergic receptors. The ubiquitous purinergic signaling maintains normal neural excitability, digestion and absorption, respiratory movement, and other complex physiological activities, and participates in cell proliferation, differentiation, migration, and death. Pathological dysregulation of purinergic signaling can result in the development of various diseases, including neurodegeneration, inflammatory reactions, and malignant tumors. The dysregulation or dysfunction of purines and purinergic receptors has been demonstrated to be closely associated with tumor progression. Compared with other subtypes of purinergic receptors, the P2X7 receptor (P2X7R) exhibits distinct characteristics (i.e., a low affinity for ATP, dual functionality upon activation, the mediation of ion channels, and nonselective pores formation) and is considered a promising target for antitumor therapy, particularly in patients with poor response to immunotherapy This review summarizes the physiological and pathological significance of purinergic signaling and purinergic receptors, analyzes their complex relationship with tumors, and proposes potential antitumor immunotherapy strategies from tumor P2X7R inhibition, tumor P2X7R overactivation, and host P2X7R activation. This review provides a reference for clinical immunotherapy and mechanism investigation.

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P2X7 receptor: a potential target for treating comorbid anxiety and depression

Liu,

Mou

et al. 2024

Purinergic Signalling

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In clinical practice, depression and anxiety frequently coexist, and they are both comorbid with somatic diseases. The P2X7R is an adenosine 5’-triphosphate (ATP)-gated non-selective cation channel that is widely expressed in immune-related cells. Under conditions of stress, chronic pain, and comorbid chronic physical illness, P2X7R activation in glial cells leads to neuroinflammation. This could contribute to the development of anxiety and depression-related emotional disturbances. Previous studies have shown that the P2X7 receptor (P2X7R) plays an important role in the pathogenesis of both anxiety and depression. Thus, the P2X7R may play a role in the comorbidity of anxiety and depression. Positron emission tomography can be used to assess the degree and location of neuroinflammation by monitoring functional and expression-related changes in P2X7R, which can facilitate clinical diagnoses and guide the treatment of patients with anxiety and depression. Moreover, single nucleotide polymorphisms (SNPs) in the P2X7R gene are associated with susceptibility to different types of psychiatric disorders. Thus, evaluating the SNPs of the P2X7R gene could enable personalized mood disorder diagnoses and treatments. If the P2X7R were set as a therapeutic target, selective P2X7R antagonists may modulate P2X7R function, thereby altering the balance of intra- and extra-cellular ATP. This could have therapeutic implications for treating anxiety and depression, as well as for pain management. According to in vitro and in vivo studies, the P2X7R plays an important role in anxiety and depression. In this review, we consider the potential of the P2X7R as a therapeutic target for comorbid anxiety and depression, and discuss the potential diagnostic and therapeutic value of this receptor.

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Emerging roles of the P2X7 receptor in cancer pain

Cited by 7 publications

References 85 publications

Neurodegenerative Diseases: Unraveling the Heterogeneity of Astrocytes

Neurodegenerative Diseases: Unraveling the Heterogeneity of Astrocytes

Purine and purinergic receptors in health and disease

P2X7 receptor: a potential target for treating comorbid anxiety and depression

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