{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T02:02:22Z","timestamp":1789783342973,"version":"4.0.1"},"reference-count":160,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T00:00:00Z","timestamp":1789689600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T00:00:00Z","timestamp":1789689600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council of Canada","doi-asserted-by":"publisher","award":["RGPIN\u20102022\u201004589"],"award-info":[{"award-number":["RGPIN\u20102022\u201004589"]}],"id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["PJT\u2010191824"],"award-info":[{"award-number":["PJT\u2010191824"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004411","name":"Heart and Stroke Foundation of Canada","doi-asserted-by":"publisher","award":["G\u201023\u20100035032"],"award-info":[{"award-number":["G\u201023\u20100035032"]}],"id":[{"id":"10.13039\/100004411","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004543","name":"China Scholarship Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004543","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"abstract":"<jats:p>\n                    Disruption of intracellular ionic homeostasis is a convergent pathological feature across diverse neurological injuries and disorders, including ischaemic and haemorrhagic stroke, hypoxic\u2013ischaemic brain injury, traumatic brain injury, epilepsy and brain tumour. Among stress\u2010activated ion channels implicated in these conditions, the transient receptor potential melastatin 7 (TRPM7) channel has emerged as a key mediator linking metabolic stress to sustained dysregulation of Ca\n                    <jats:sup>2+<\/jats:sup>\n                    , Mg\n                    <jats:sup>2+<\/jats:sup>\n                    and Zn\n                    <jats:sup>2+<\/jats:sup>\n                    signalling and downstream injury cascades. TRPM7 is a unique bifunctional protein composed of a divalent cation\u2010permeable ion channel fused with a C\u2010terminal\n                    <jats:italic>\u03b1<\/jats:italic>\n                    \u2010kinase domain, enabling integration of ionic flux with intracellular signalling. Accumulating evidence from cellular, electrophysiological and in vivo studies demonstrates that TRPM7 contributes causally to neuronal injury, vascular dysfunction, network hyperexcitability and tumour cell malignancy across disease models. Natural products have historically played a central role in ion channel pharmacology, and growing evidence has identified structurally diverse natural product\u2010derived compounds as modulators of TRPM7 channel. In this review, we synthesize mechanistic and pharmacological evidence supporting TRPM7 as a tractable therapeutic target, with particular focus on representative natural product\u2010derived TRPM7 channel inhibitors including carvacrol, waixenicin A and xyloketal B, which span a spectrum of potency, selectivity and mechanistic complexity. We further discuss key translational challenges associated with targeting TRPM7 in neurological injury, including target selectivity, essential physiological roles, CNS exposure and context\u2010dependent disease effects. Collectively, available evidence positions TRPM7 as a pharmacologically actionable target and highlights the potential of natural product scaffolds to guide the development of next\u2010generation TRPM7\u2010directed therapies for neurological injury.\n                  <\/jats:p>","DOI":"10.1111\/bph.70667","type":"journal-article","created":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T01:10:30Z","timestamp":1789780230000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Natural product\u2010derived TRPM7 channel inhibitors in neurological injury: Mechanisms, pharmacological potential and translational challenges"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-7165-4278","authenticated-orcid":false,"given":"Xinyang","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Surgery, Temerty Faculty of Medicine University of Toronto  Toronto Ontario Canada"},{"name":"Department of Physiology, Temerty Faculty of Medicine University of Toronto  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-7031-4614","authenticated-orcid":false,"given":"Hio Lam","family":"Ho","sequence":"additional","affiliation":[{"name":"Department of Surgery, Temerty Faculty of Medicine University of Toronto  Toronto Ontario Canada"},{"name":"Department of Physiology, Temerty Faculty of Medicine University of Toronto  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9409-3030","authenticated-orcid":false,"given":"F. 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