TREM2 mutations implicated in neurodegeneration impair cell surface transport and phagocytosis
| العنوان: | TREM2 mutations implicated in neurodegeneration impair cell surface transport and phagocytosis |
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| المؤلفون: | Hanne Struyfs, John Hardy, Marc Suárez-Calvet, Jean-Jacques Martin, Julie van der Zee, Ebba Lohmann, Andrea Wenninger-Weinzierl, Yoshinori Yamanishi, Juan Fortea, Raquel Sánchez-Valle, Alberto Lleó, Nadine Pettkus, Asli Demirtas-Tatlidede, Fargol Mazaheri, Christine Van Broeckhoven, Henrik Zetterberg, Michael Willem, Michael T. Heneka, Daniel Alcolea, Kristel Sleegers, Gernot Kleinberger, Christian Haass, Sven Lammich, Marco Colonna, Elise Cuyvers, José Luis Molinuevo, Anna Antonell, Hakan Gurvit, Alfredo Ramirez, Tony Wyss-Coray, Sebastiaan Engelborghs, Sabina Tahirovic, Eva Czirr |
| المساهمون: | Clinical sciences, Neurology, Pathologic Biochemistry and Physiology |
| المصدر: | Science translational medicine Science translational medicine 6(243), 243ra86-243ra86 (2014). doi:10.1126/scitranslmed.3009093 Science Translational Medicine r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau instname |
| سنة النشر: | 2014 |
| مصطلحات موضوعية: | genetics [Alzheimer Disease], Frontotemporal Dementia/genetics, genetics [Membrane Glycoproteins], Neurodegenerative Diseases/genetics, genetics [Receptors, Immunologic], Amyotrophic lateral sclerosis, Receptors, Immunologic, genetics [Frontotemporal Dementia], Cells, Cultured, Medicine(all), Membrane Glycoproteins, Microglia, Receptors, Immunologic/genetics, Neurodegeneration, Neurodegenerative Diseases, General Medicine, Frontotemporal lobar degeneration, Biological Transport/genetics, physiology [Biological Transport], medicine.anatomical_structure, Frontotemporal Dementia, ddc:500, physiology [Phagocytosis], medicine.symptom, Phagocytosis/genetics, Frontotemporal dementia, Inflammation, Enzyme-Linked Immunosorbent Assay, Biology, Cell Line, Phagocytosis, Alzheimer Disease, mental disorders, medicine, Humans, genetics [Phagocytosis], Alzheimer Disease/genetics, genetics [Biological Transport], Innate immune system, TREM2 protein, human, TREM2, nutritional and metabolic diseases, Biological Transport, Membrane Glycoproteins/genetics, medicine.disease, nervous system diseases, genetics [Neurodegenerative Diseases], Immunology, Mutation, Human medicine |
| الوصف: | Genetic variants in the triggering receptor expressed on myeloid cells 2 (TREM2) have been linked to Nasu-Hakola disease, Alzheimer's disease (AD), Parkinson's disease, amyotrophic lateral sclerosis, frontotemporal dementia (FTD), and FTD-like syndrome without bone involvement. TREM2 is an innate immune receptor preferentially expressed by microglia and is involved in inflammation and phagocytosis. Whether and how TREM2 missense mutations affect TREM2 function is unclear. We report that missense mutations associated with FTD and FTD-like syndrome reduce TREM2 maturation, abolish shedding by ADAM proteases, and impair the phagocytic activity of TREM2-expressing cells. As a consequence of reduced shedding, TREM2 is virtually absent in the cerebrospinal fluid (CSF) and plasma of a patient with FTD-like syndrome. A decrease in soluble TREM2 was also observed in the CSF of patients with AD and FTD, further suggesting that reduced TREM2 function may contribute to increased risk for two neurodegenerative disorders. |
| اللغة: | English |
| تدمد: | 1946-6234 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ed9a26c869d37ded182b204226376214Test https://hdl.handle.net/10067/1186390151162165141Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....ed9a26c869d37ded182b204226376214 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19466234 |
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