{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRecent studies have demonstrated that pannexin channels – notably those formed by Panx1 and Panx2 – are integral to mediating intercellular communication and contributing to pathological processes such as ischemic brain injury. In experimental models of cerebral ischemia, dual Panx1/Panx2 knockout mice exhibit reduced neuronal channel function and impaired dye release, which correlates with decreased infarct sizes and improved sensorimotor outcomes. These observations indicate that while some glial and inflammatory responses (e.g., IL‑1β release and astrocytic hemichannel function) remain unaffected by loss of these channels, their neuronal expression contributes markedly to brain damage under ischemic conditions."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nDevelopmental expression analyses have revealed that pannexins are widely distributed throughout the nervous system, yet their expression is both spatially and temporally regulated. For instance, Panx1 is robustly expressed in the embryonic brain and declines in adulthood, whereas Panx2 displays an opposite pattern with increased postnatal expression. These proteins are found in diverse neuronal populations including retinal ganglion cells, cochlear supporting cells, olfactory neurons, and even in non‐neuronal structures of the lens. Such distribution patterns suggest critical roles in establishing and maintaining neural circuitry as well as in sensory processing."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "3", "end_ref": "8"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAt the molecular level, pannexins are subject to complex regulation – including glycosylation, post‐translational modifications, and protein–protein interactions – which collectively influence their cellular trafficking and channel function. The formation of heteromeric complexes (for example, between Panx1 and Panx2 or Panx3) is glycosylation‑dependent and affects their plasma membrane targeting. In neural progenitor cells, distinct post‑translational modifications of Panx2 regulate the timing of neuronal differentiation, while in peripheral tissues such as pancreatic β‑cells and epidermal keratinocytes, pannexins modulate apoptotic responses under pro‑inflammatory or stress conditions. These multifaceted roles underscore the diverse contribution of pannexins in both normal tissue homeostasis and in response to cellular injury."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "9", "end_ref": "13"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Panagiotis Bargiotas, Antje Krenz, Sheriar G Hormuzdi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Pannexins in ischemia-induced neurodegeneration."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1018262108"}], "href": "https://doi.org/10.1073/pnas.1018262108"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22147915"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22147915"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Panagiotis Bargiotas, Antje Krenz, Hannah Monyer, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Functional outcome of pannexin-deficient mice after cerebral ischemia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Channels (Austin) (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4161/chan.22315"}], "href": "https://doi.org/10.4161/chan.22315"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23111424"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23111424"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Angelika Vogt, Sheriar G Hormuzdi, Hannah Monyer "}, {"type": "b", "children": [{"type": "t", "text": "Pannexin1 and Pannexin2 expression in the developing and mature rat brain."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Brain Res Mol Brain Res (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.molbrainres.2005.08.002"}], "href": "https://doi.org/10.1016/j.molbrainres.2005.08.002"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16143426"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16143426"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Galina Dvoriantchikova, Dmitry Ivanov, Yuri Panchin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Expression of pannexin family of proteins in the retina."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FEBS Lett (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.febslet.2006.03.026"}], "href": "https://doi.org/10.1016/j.febslet.2006.03.026"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16616526"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16616526"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Galina Dvoriantchikova, Dmitry Ivanov, Anna Pestova, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Molecular characterization of pannexins in the lens."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Vis (2006)"}]}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17149368"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17149368"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Wenxue Tang, Shoeb Ahmad, Valery I Shestopalov, et al. 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