title: [Molecular Pathogenesis of Nasu-Hakola Disease Brain Lesions].
abstract: Nasu-Hakola disease (NHD) is a rare intractable autosomal recessive disorder, characterized by pathological bone fractures and progressive dementia owing to multifocal bone cysts and leukoencephalopathy, caused by various genetic mutations of either DAP12 or TREM2. Loss-of-function of TREM2-DAP12, constituting a signaling complex on osteoclasts and microglia, plays a central role in the pathogenesis of NHD. Recently, NHD has been recognized as the disease entity designated "microgliopathy". However, at present, TREM2-specific ligands in microglia and the precise molecular mechanism underlying leukoencephalopathy remain to be investigated in order to establish an effective molecular targeted therapy for NHD.
authors.affiliation: Department of Bioinformatics and Molecular Neuropathology, Meiji Pharmaceutical University.
authors.forename: Jun-Ichi
authors.initials: J
authors.lastname: Satoh
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism*; D006801:Humans; D008060:Lipodystrophy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D008562:Membrane Glycoproteins / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D010009:Osteochondrodysplasias / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D011485:Protein Binding; D011971:Receptors, Immunologic / Q000378:metabolism; D015398:Signal Transduction; D013344:Subacute Sclerosing Panencephalitis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D011971:Receptors, Immunologic; C498715:TREM2 protein, human; C110546:TYROBP protein, human