{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T14:12:40Z","timestamp":1780495960687,"version":"3.54.1"},"reference-count":56,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2020,9,4]],"date-time":"2020-09-04T00:00:00Z","timestamp":1599177600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000646","name":"Japan Society for the Promotion of Science London","doi-asserted-by":"publisher","award":["JP 16k09685"],"award-info":[{"award-number":["JP 16k09685"]}],"id":[{"id":"10.13039\/501100000646","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Infected or damaged tissues release multiple \u201calert\u201d molecules such as alarmins and damage-associated molecular patterns (DAMPs) that are recognized by innate immune receptors, and induce tissue inflammation, regeneration, and repair. Recently, an extract from inflamed rabbit skin inoculated with vaccinia virus (Neurotropin\u00ae, NTP) was found to induce infarct tolerance in mice receiving permanent ischemic attack to the middle cerebral artery. Likewise, we report herein that NTP prevented the neurite retraction in PC12 cells by nerve growth factor (NGF) deprivation. This effect was accompanied by interaction of Fyn with high-affinity NGF receptor TrkA. Sucrose density gradient subcellular fractionation of NTP-treated cells showed heretofore unidentified membrane fractions with a high-buoyant density containing Trk, B subunit of cholera toxin-bound ganglioside, flotillin-1 and Fyn. Additionally, these new membrane fractions also contained Toll-like receptor 4 (TLR4). Inhibition of TLR4 function by TAK-242 prevented the formation of these unidentified membrane fractions and suppressed neuroprotection by NTP. These observations indicate that NTP controls TrkA-mediated signaling through the formation of clusters of new membrane microdomains, thus providing a platform for crosstalk between neurotrophic and innate immune receptors. Neuroprotective mechanisms through the interaction with innate immune systems may provide novel mechanism for neuroprotection.<\/jats:p>","DOI":"10.3390\/ijms21186456","type":"journal-article","created":{"date-parts":[[2020,9,4]],"date-time":"2020-09-04T11:24:24Z","timestamp":1599218664000},"page":"6456","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Neuroprotection by Neurotropin through Crosstalk of Neurotrophic and Innate Immune Receptors in PC12 Cells"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5737-2401","authenticated-orcid":false,"given":"Yu","family":"Fukuda","sequence":"first","affiliation":[{"name":"Department of Neurology and Neuroscience, Fujita Health University Hospital, Toyoake, Aichi 470-1192, Japan"},{"name":"Nippon Zoki Pharmaceutical Co., Ltd., Osaka 564-0052, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuki","family":"Nakajima","sequence":"additional","affiliation":[{"name":"Center for joint research facilities support, Research Promotion and Support Headquarters, Fujita Health University School of Medicine, Toyoake, Aichi 470-1192, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7712-8481","authenticated-orcid":false,"given":"Tatsuro","family":"Mutoh","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neuroscience, Fujita Health University Hospital, Toyoake, Aichi 470-1192, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,9,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1038\/350158a0","article-title":"Tyrosine phosphorylation and tyrosine kinase activity of the trk proto-oncogene product induced by NGF","volume":"350","author":"Kaplan","year":"1991","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1126\/science.1850549","article-title":"The Trk proto-oncogene product: A signal transducing receptor for nerve growth factor","volume":"252","author":"Kaplan","year":"1991","journal-title":"Science"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1016\/0896-6273(92)90023-7","article-title":"Neurotrophin receptors: A window into neuronal differentiation","volume":"9","author":"Chao","year":"1992","journal-title":"Neuron"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1146\/annurev.neuro.24.1.677","article-title":"Neurotrophins: Roles in neuronal development and function","volume":"24","author":"Huang","year":"2001","journal-title":"Annu. 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