{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T15:35:24Z","timestamp":1772638524816,"version":"3.50.1"},"reference-count":35,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2011,10,10]],"date-time":"2011-10-10T00:00:00Z","timestamp":1318204800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neuropathology"],"published-print":{"date-parts":[[2012,4]]},"abstract":"<jats:p>Nasu\u2010Hakola disease (NHD) is a rare autosomal recessive disorder, characterized by progressive presenile dementia and formation of multifocal bone cysts, caused by a loss\u2010of\u2010function mutation of DNAX\u2010activation protein 12 (DAP12) or triggering receptor expressed on myeloid cells 2 (TREM2). TREM2 and DAP12 constitute a receptor\/adaptor complex on myeloid cells. The post\u2010receptor signals are transmitted via rapid phosphorylation of the immunoreceptor tyrosine\u2010based activating motif (ITAM) of DAP12, mediated by Src protein tyrosine kinases, followed by binding of phosphorylated ITAM to Src homology 2 (SH2) domains of spleen tyrosine kinase (Syk), resulting in autophosphorylation of the activation loop of Syk. To elucidate the molecular mechanism underlying the pathogenesis of NHD, we investigated Syk expression and activation in the frontal cortex and the hippocampus of three NHD and eight control brains by immunohistochemistry. In NHD brains, the majority of neurons expressed intense immunoreactivities for Syk and Y525\/Y526\u2010phosphorylated Syk (pSyk) chiefly located in the cytoplasm, while more limited populations of neurons expressed Src. The levels of pSyk expression were elevated significantly in NHD brains compared with control brains. In both NHD and control brains, substantial populations of microglia and macrophages expressed pSyk, while the great majority of reactive astrocytes and myelinating oligodendrocytes did not express pSyk, Syk or Src. These observations indicate that neuronal expression of pSyk was greatly enhanced in the cerebral cortex and the hippocampus of NHD brains, possibly via non\u2010TREM2\/DAP12 signaling pathways involved in Syk activation.<\/jats:p>","DOI":"10.1111\/j.1440-1789.2011.01256.x","type":"journal-article","created":{"date-parts":[[2011,10,10]],"date-time":"2011-10-10T16:39:38Z","timestamp":1318264778000},"page":"149-157","source":"Crossref","is-referenced-by-count":28,"title":["Phosphorylated Syk expression is enhanced in Nasu\u2010Hakola disease 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