P2X Receptor-Dependent Modulation of Mast Cell and Glial Cell Activities in Neuroinflammation

Salcman, Barbora; Affleck, Karen; Bulfone–Paus∥, Silvia

doi:10.3390/cells10092282

Cited by 6 publications

(3 citation statements)

References 177 publications

(212 reference statements)

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“…In the brain, MCs can be found on the abluminal sides of blood vessels, where they interact with neurons and glial cells [ 41 ]. Different receptors—such as toll-like receptor (TLR) 2 [ 42 ], TLR4 [ 42 ] or P2X receptors [ 43 ]—induce MC degranulation with the consequent release of various mediators, such as biogenic amines, cytokines, neuropeptides, growth factors or ATP [ 42 ]. Mediators secreted by MCs promote nociceptor activation and hypersensitization, both directly—via pro-nociceptor mediators’ production [ 44 ]—and indirectly—inducing neuropeptide release [ 42 ].…”

Section: Pathophysiology Of Pain In Fm Syndromementioning

confidence: 99%

Pain Biomarkers in Fibromyalgia Syndrome: Current Understanding and Future Directions

Favretti

Iannuccelli

Franco

2023

IJMS

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Fibromyalgia is a complex and heterogeneous clinical syndrome, mainly characterized by the presence of widespread pain, possibly associated with a variety of other symptoms. Fibromyalgia can have an extremely negative impact on the psychological, physical and social lives of people affected, sometimes causing patients to experience dramatically impaired quality of life. Nowadays, the diagnosis of fibromyalgia is still clinical, thus favoring diagnostic uncertainties and making its clear identification challenging to establish, especially in primary care centers. These difficulties lead patients to undergo innumerable clinical visits, investigations and specialist consultations, thus increasing their stress, frustration and even dissatisfaction. Unfortunately, research over the last 25 years regarding a specific biomarker for the diagnosis of fibromyalgia has been fruitless. The discovery of a reliable biomarker for fibromyalgia syndrome would be a critical step towards the early identification of this condition, not only reducing patient healthcare utilization and diagnostic test execution but also providing early intervention with guideline-based treatments. This narrative article reviews different metabolite alterations proposed as possible biomarkers for fibromyalgia, focusing on their associations with clinical evidence of pain, and highlights some new, promising areas of research in this context. Nevertheless, none of the analyzed metabolites emerge as sufficiently reliable to be validated as a diagnostic biomarker. Given the complexity of this syndrome, in the future, a panel of biomarkers, including subtype-specific biomarkers, could be considered as an interesting alternative research area.

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Section: Pathophysiology Of Pain In Fm Syndromementioning

confidence: 99%

Pain Biomarkers in Fibromyalgia Syndrome: Current Understanding and Future Directions

Favretti

Iannuccelli

Franco

2023

IJMS

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“…These receptors play an important role in regulating MC activities, such as calcium influx and degranulation that results in the release of many pre-stored inflammatory mediators ( Bulanova and Bulfone-Paus, 2010 ). Inflammatory mediators include IL-1β, Nuclear factor kappa B (NF-κB), tumor necrosis factor α (TNF-α), serotonin, and kinins, along with the synthesis and secretion of an array of cytokines, chemokines, prostaglandins, leukotrienes, and growth and angiogenesis factors (i.e., platelet-derived growth factor and VEGF) ( Galli and Tsai, 2008 ; Bulanova and Bulfone-Paus, 2010 ; Kurashima et al, 2012 ; Theoharides et al, 2012 ; Shieh et al, 2014 ; Salcman et al, 2021 ). These MC components can modulate the activity of cells in their proximity and lead to the generation of reactive oxygen species (ROS), promotion of chemotaxis, altered phagocytosis, degradation of underlying extracellular matrix (ECM), and other events contributing to an overall increase in inflammation ( Bhutto et al, 2016 ; Kempuraj et al, 2016 ; Caraffa et al, 2018 ).…”

Section: Purinergic Signaling In the Retinamentioning

confidence: 99%

Purinergic signaling via P2X receptors and mechanisms of unregulated ATP release in the outer retina and age-related macular degeneration

Molcak,

Jiang,

Campbell

et al. 2023

Front. Neurosci.

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Age-related macular degeneration (AMD) is a chronic and progressive inflammatory disease of the retina characterized by photoceptor loss and significant central visual impairment due to either choroidal neovascularization or geographic atrophy. The pathophysiology of AMD is complex and multifactorial, driven by a combination of modifiable and non-modifiable risk factors, molecular mechanisms, and cellular processes that contribute to overall disease onset, severity, and progression. Unfortunately, due to the structural, cellular, and pathophysiologic complexity, therapeutic discovery is challenging. While purinergic signaling has been investigated for its role in the development and treatment of ocular pathologies including AMD, the potential crosstalk between known contributors to AMD, such as the complement cascade and inflammasome activation, and other biological systems, such as purinergic signaling, have not been fully characterized. In this review, we explore the interactions between purinergic signaling, ATP release, and known contributors to AMD pathogenesis including complement dysregulation and inflammasome activation. We begin by identifying what is known about purinergic receptors in cell populations of the outer retina and potential sources of extracellular ATP required to trigger purinergic receptor activation. Next, we examine evidence in the literature that the purinergic system accelerates AMD pathogenesis leading to apoptotic and pyroptotic cell death in retinal cells. To fully understand the potential role that purinergic signaling plays in AMD, more research is needed surrounding the expression, distribution, functions, and interactions of purinergic receptors within cells of the outer retina as well as potential crosstalk with other systems. By determining how these processes are affected in the context of purinergic signaling, it will improve our understanding of the mechanisms that drive AMD pathogenesis which is critical in developing treatment strategies that prevent or slow progression of the disease.

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“…Hence, MCs degranulation and the release of histamine and TNF-α activate microglia [96]. Moreover, during inflammation, ATP derived from MCs activates purinergic P2 receptors in the microglia leading to IL-33 secretion [98]. In turn, IL-33 causes MCs to release IL-6, IL-13 and the monocyte chemoattractant protein-1 (MCP-1), which also regulates microglial activity.…”

Section: Immunity and Inflammation As Therapeutic Targetsmentioning

confidence: 99%

Impact of New Drugs for Therapeutic Intervention in Alzheimer’s Disease

Olloquequi¹,

Ettcheto²,

Cano³

et al. 2022

Front. Biosci. (Landmark Ed)

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The increases in population ageing and growth are leading to a boosting in the number of people living with dementia, Alzheimer's disease (AD) being the most common cause. In spite of decades of intensive research, no cure for AD has been found yet. However, some treatments that may change disease progression and help control symptoms have been proposed. Beyond the classical hypotheses of AD etiopathogenesis, i.e., amyloid beta peptide (Aβ) accumulation and tau hyperphosphorylation, a trend in attributing a key role to other molecular mechanisms is prompting the study of different therapeutic targets. Hence, drugs designed to modulate inflammation, insulin resistance, synapses, neurogenesis, cardiovascular factors and dysbiosis are shaping a new horizon in AD treatment. Within this frame, an increase in the number of candidate drugs for disease modification treatments is expected, as well as a focus on potential combinatory multidrug strategies.The present review summarizes the latest advances in drugs targeting Aβ and tau as major contributors to AD pathophysiology. In addition, it introduces the most important drugs in clinical studies targeting alternative mechanisms thought to be involved in AD's neurodegenerative process.

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P2X Receptor-Dependent Modulation of Mast Cell and Glial Cell Activities in Neuroinflammation

Cited by 6 publications

References 177 publications

Pain Biomarkers in Fibromyalgia Syndrome: Current Understanding and Future Directions

Pain Biomarkers in Fibromyalgia Syndrome: Current Understanding and Future Directions

Purinergic signaling via P2X receptors and mechanisms of unregulated ATP release in the outer retina and age-related macular degeneration

Impact of New Drugs for Therapeutic Intervention in Alzheimer’s Disease

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