Nanobodies as probes to investigate purinergic signaling

Eggers, Marie; Rühl, Felix; Haag, Friedrich; Koch-Nolte, Friedrich

doi:10.1016/j.bcp.2020.114394

Cited by 5 publications

(1 citation statement)

References 75 publications

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“…In addition to small chemical molecules, nanobodies have also been developed for the functional exclusion of P2X7Rs [ 71 , 72 ]. They are derived from heavy chain antibodies that naturally occur in camelids and display a propensity to bind functional epitopes not accessible to conventional antibodies.…”

Section: P2x7rs Are Potential Targets For the Therapy Of Psychiatric ...mentioning

confidence: 99%

A Possible Causal Involvement of Neuroinflammatory, Purinergic P2X7 Receptors in Psychiatric Disorders

Zhang

Yin

Rubini

et al. 2022

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P2X7 receptors (Rs) are prominent members of the P2XR family which after binding ATP open non-selective cationic channels allowing the transmembrane passage of Na+, Ca2+ and K+. Long-lasting and repetitive stimulation of the receptor by its agonist leads to the formation of large membrane pores permeable for organic cations of up to 900 Da molecular size. These pores are believed to play a role in apoptosis and inflammation. P2X7Rs are located primarily at peripheral macrophages and at microglial cells, the resident macrophages of the CNS. The co-activation of toll-like receptors 4 (TLR4) by lipopolysaccharide, a constituent of the cell membrane of gram negative bacteria, and the P2X7R by ATP leads to the generation and release of the pro-inflammatory cytokines interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α. These cytokines together with the microglial release of chemokines, reactive oxygen and nitrogen species, proteases, and also the excitotoxic glutamate results in neurodegeneration. P2X7Rs were found not only to amplify various neurodegenerative illnesses such as Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, and multiple sclerosis, but also to participate in a range of psychiatric diseases such as major depression, bipolar disorder, schizophrenia and autism spectrum disorder. Based on the prevention/reversal of neuroinflammation, pharmacological antagonists of P2X7Rs and their genetic deletion in animal experiments counteracts these deleterious psychiatric conditions. Hence, brain penetrant P2X7R antagonists are potential therapeutics for psychiatric diseases, although the available evidence still needs to be extended and validated by further clinical data.

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Section: P2x7rs Are Potential Targets For the Therapy Of Psychiatric ...mentioning

confidence: 99%