P2X4 receptor participates in autophagy regulation in Parkinson's disease

Zhang, Xue; Wang, Jing; Gao, Jinzhao; Zhang, Xiaona; Dou, Kaixin; Shi, Wan-Da; Xie, Anmu

doi:10.4103/1673-5374.313053

Cited by 21 publications

(1 citation statement)

References 42 publications

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“…In the experimental autoimmune encephalomyelitis (EAE) model, P2X4 receptors signaling inhibition or P2X4 knockout increases pro-inflammatory gene expression in microglia ( Zabala et al, 2018 ). Moreover, P2X4 receptor protein is increased in the SN of the PD rat model and P2X4 receptor activation is involved in DA neuronal autophagy inhibition ( Zhang X. et al, 2021 ), indicating that P2X4 receptor might serve as a potential way for the treatment of PD.…”

Section: Role Of Purinergic Receptors In Microglial Activation Of Parkinson’s Diseasementioning

confidence: 99%

Role of G Protein-Coupled Receptors in Microglial Activation: Implication in Parkinson’s Disease

Chen

et al. 2021

Front. Aging Neurosci.

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Parkinson’s disease (PD) is one of the prevalent neurodegenerative diseases associated with preferential loss of dopaminergic (DA) neurons in the substantia nigra compacta (SNc) and accumulation of α-synuclein in DA neurons. Even though the precise pathogenesis of PD is not clear, a large number of studies have shown that microglia-mediated neuroinflammation plays a vital role in the process of PD development. G protein-coupled receptors (GPCRs) are widely expressed in microglia and several of them act as regulators of microglial activation upon corresponding ligands stimulations. Upon α-synuclein insults, microglia would become excessively activated through some innate immune receptors. Presently, as lack of ideal drugs for treating PD, certain GPCR which is highly expressed in microglia of PD brain and mediates neuroinflammation effectively could be a prospective source for PD therapeutic intervention. Here, six kinds of GPCRs and two types of innate immune receptors were introduced, containing adenosine receptors, purinergic receptors, metabotropic glutamate receptors, adrenergic receptors, cannabinoid receptors, and melatonin receptors and their roles in neuroinflammation; we highlighted the relationship between these six GPCRs and microglial activation in PD. Based on the existing findings, we tried to expound the implication of microglial GPCRs-regulated neuroinflammation to the pathophysiology of PD and their potential to become a new expectation for clinical therapeutics.

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Section: Role Of Purinergic Receptors In Microglial Activation Of Parkinson’s Diseasementioning

confidence: 99%

Role of G Protein-Coupled Receptors in Microglial Activation: Implication in Parkinson’s Disease

Chen

et al. 2021

Front. Aging Neurosci.

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Purinergic Signaling in Parkinson’s Disease

Silva

Ferreira

Glaser

et al. 2023

Purinergic Signaling in Neurodevelopment, Neuroinflammation and Neurodegeneration

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Preparation and preliminary evaluation of a tritium-labeled allosteric P2X4 receptor antagonist

Nagel,

Törmäkangas,

Kuokkanen

et al. 2024

Purinergic Signalling

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P2X4 receptors are ATP-gated cation channels that were proposed as novel drug targets due to their role in inflammation and neuropathic pain. Only few potent and selective P2X4 receptor antagonists have been described to date. Labeled tool compounds suitable for P2X4 receptor binding studies are lacking. Here, we present a novel allosteric P2X4 receptor antagonist possessing high potency in the low nanomolar range. We describe its tritium-labeling resulting in the P2X4-selective radiotracer [3H]PSB-OR-2020 with high specific activity (45 Ci/mmol; 1.67 TBq/mmol). A radioligand binding assay was developed using human embryonic kidney (HEK293) cell membranes recombinantly expressing the human P2X4 receptor. Competition binding studies with structurally diverse P2X4 receptor antagonists revealed different allosteric binding sites indicating that the new class of P2X4 receptor antagonists, to which PSB-OR-2020 belongs, interacts with an unprecedented allosteric site. [3H]PSB-OR-2020 may become a useful tool for research on P2X4 receptors and for promoting drug development.

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P2X4 receptor participates in autophagy regulation in Parkinson's disease

Cited by 21 publications

References 42 publications

Role of G Protein-Coupled Receptors in Microglial Activation: Implication in Parkinson’s Disease

Role of G Protein-Coupled Receptors in Microglial Activation: Implication in Parkinson’s Disease

Purinergic Signaling in Parkinson’s Disease

Preparation and preliminary evaluation of a tritium-labeled allosteric P2X4 receptor antagonist

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