Src family kinases activity is required for transmitting purinergic P2X7 receptor signaling in cortical spreading depression and neuroinflammation

Nie, Lingdi; Ma, Dongqing; Quinn, John P.; Wang, Minyan

doi:10.1186/s10194-021-01359-8

Cited by 13 publications

(7 citation statements)

References 61 publications

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“…Both ATP and glutamate are bound by P2X7 receptors. In cultured and in situ astrocytes, activating these receptors causes ATP uptake and glutamate release at the same time [ 215 ]. Radiolabeled tracers were used to establish the release of L-glutamate and D-aspartate through P2X7 channels [ 214 ].…”

Section: Major Participants In Astrocytic Glutamatergic Transmission ...mentioning

confidence: 99%

Astrocytic Glutamatergic Transmission and Its Implications in Neurodegenerative Disorders

Satarker

Bojja

Gurram

et al. 2022

Cells

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Several neurodegenerative disorders involve impaired neurotransmission, and glutamatergic neurotransmission sets a prototypical example. Glutamate is a predominant excitatory neurotransmitter where the astrocytes play a pivotal role in maintaining the extracellular levels through release and uptake mechanisms. Astrocytes modulate calcium-mediated excitability and release several neurotransmitters and neuromodulators, including glutamate, and significantly modulate neurotransmission. Accumulating evidence supports the concept of excitotoxicity caused by astrocytic glutamatergic release in pathological conditions. Thus, the current review highlights different vesicular and non-vesicular mechanisms of astrocytic glutamate release and their implication in neurodegenerative diseases. As in presynaptic neurons, the vesicular release of astrocytic glutamate is also primarily meditated by calcium-mediated exocytosis. V-ATPase is crucial in the acidification and maintenance of the gradient that facilitates the vesicular storage of glutamate. Along with these, several other components, such as cystine/glutamate antiporter, hemichannels, BEST-1, TREK-1, purinergic receptors and so forth, also contribute to glutamate release under physiological and pathological conditions. Events of hampered glutamate uptake could promote inflamed astrocytes to trigger repetitive release of glutamate. This could be favorable towards the development and worsening of neurodegenerative diseases. Therefore, across neurodegenerative diseases, we review the relations between defective glutamatergic signaling and astrocytic vesicular and non-vesicular events in glutamate homeostasis. The optimum regulation of astrocytic glutamatergic transmission could pave the way for the management of these diseases and add to their therapeutic value.

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Section: Major Participants In Astrocytic Glutamatergic Transmission ...mentioning

confidence: 99%

Astrocytic Glutamatergic Transmission and Its Implications in Neurodegenerative Disorders

Satarker

Bojja

Gurram

et al. 2022

Cells

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“…Nevertheless, regardless of how the P2X7R contributes to AD, these results strongly suggest that P2X7R is involved in memory loss and, consequently, identify the P2X7R as a possible therapeutic target to counteract cognitive decline seen, for example, in epilepsy [188]. Migraine is another common CNS disease associated with epilepsy, where P2X7R activation has been suggested to contribute to the pathology of the disease [189]. Cardiovascular conditions are among non-CNS diseases associated with epilepsy where P2X7R activation has also been suggested as a contributor.…”

Section: P2x7rs and Other Common Co-morbidities Associated With Epilepsymentioning

confidence: 97%

Beyond Seizure Control: Treating Comorbidities in Epilepsy via Targeting of the P2X7 Receptor

Gil

Smith

Tang

et al. 2022

IJMS

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Epilepsy is one of the most common chronic diseases of the central nervous system (CNS). Treatment of epilepsy remains, however, a clinical challenge with over 30% of patients not responding to current pharmacological interventions. Complicating management of treatment, epilepsy comes with multiple comorbidities, thereby further reducing the quality of life of patients. Increasing evidence suggests purinergic signalling via extracellularly released ATP as shared pathological mechanisms across numerous brain diseases. Once released, ATP activates specific purinergic receptors, including the ionotropic P2X7 receptor (P2X7R). Among brain diseases, the P2X7R has attracted particular attention as a therapeutic target. The P2X7R is an important driver of inflammation, and its activation requires high levels of extracellular ATP to be reached under pathological conditions. Suggesting the therapeutic potential of drugs targeting the P2X7R for epilepsy, P2X7R expression increases following status epilepticus and during epilepsy, and P2X7R antagonism modulates seizure severity and epilepsy development. P2X7R antagonism has, however, also been shown to be effective in treating conditions most commonly associated with epilepsy such as psychiatric disorders and cognitive deficits, which suggests that P2X7R antagonisms may provide benefits beyond seizure control. This review summarizes the evidence suggesting drugs targeting the P2X7R as a novel treatment strategy for epilepsy with a particular focus of its potential impact on epilepsy-associated comorbidities.

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“…Subtle, but noteworthy, differences may exist in the occurrence and development of different NDs. Studies have shown that P2 × 7R/SFK signaling may be involved in the pathophysiology of cortical-spreading-depression-associated migraine [ 45 ].…”

Section: Electrophysiology and Related Signaling Pathways Of P2 × 7rmentioning

confidence: 99%

Role of the P2 × 7 receptor in neurodegenerative diseases and its pharmacological properties

Hu,

Luo,

Zhu

et al. 2023

Cell Biosci

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Neurodegenerative diseases seriously affect patients’ physical and mental health, reduce their quality of life, and impose a heavy burden on society. However, their treatment remains challenging. Therefore, exploring factors potentially related to the pathogenesis of neurodegenerative diseases and improving their diagnosis and treatment are urgently needed. Recent studies have shown that P2 × 7R plays a crucial role in regulating neurodegenerative diseases caused by neuroinflammation. P2 × 7R is an adenosine 5′-triphosphate ligand-gated cation channel receptor present in most tissues of the human body. An increase in P2 × 7R levels can affect the progression of neurodegenerative diseases, and the inhibition of P2 × 7R can alleviate neurodegenerative diseases. In this review, we comprehensively describe the biological characteristics (structure, distribution, and function) of this gene, focusing on its potential association with neurodegenerative diseases, and we discuss the pharmacological effects of drugs (P2 × 7R inhibitors) used to treat neurodegenerative diseases.

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Src family kinases activity is required for transmitting purinergic P2X7 receptor signaling in cortical spreading depression and neuroinflammation

Cited by 13 publications

References 61 publications

Astrocytic Glutamatergic Transmission and Its Implications in Neurodegenerative Disorders

Astrocytic Glutamatergic Transmission and Its Implications in Neurodegenerative Disorders

Beyond Seizure Control: Treating Comorbidities in Epilepsy via Targeting of the P2X7 Receptor

Role of the P2 × 7 receptor in neurodegenerative diseases and its pharmacological properties

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