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TREM2 Is a Receptor for ß-Amyloid that Mediates Microglial Function.
Zhao, Yingjun; Wu, Xilin; Li, Xiaoguang; Jiang, Lu-Lin; Gui, Xun; Liu, Yan; Sun, Yu; Zhu, Bing; Piña-Crespo, Juan C; Zhang, Muxian; Zhang, Ningyan; Chen, Xiaochun; Bu, Guojun; An, Zhiqiang; Huang, Timothy Y; Xu, Huaxi.
Afiliação
  • Zhao Y; Neuroscience Initiative, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA.
  • Wu X; Neuroscience Initiative, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA; Department of Neurology, Union Hospital, and Fujian Key Laboratory of Molecular Neurology, Fujian Medical University, Fuzhou, Fujian 350001, China.
  • Li X; Neuroscience Initiative, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA.
  • Jiang LL; Neuroscience Initiative, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA.
  • Gui X; Texas Therapeutics Institute, The Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
  • Liu Y; Neuroscience Initiative, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA; Fujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, Institute of Neuroscience, College of Medicine, Xiamen University, Xiamen, Fujian 361102, China.
  • Sun Y; Neuroscience Initiative, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA.
  • Zhu B; Neuroscience Initiative, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA.
  • Piña-Crespo JC; Neuroscience Initiative, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA.
  • Zhang M; Fujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, Institute of Neuroscience, College of Medicine, Xiamen University, Xiamen, Fujian 361102, China.
  • Zhang N; Texas Therapeutics Institute, The Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
  • Chen X; Department of Neurology, Union Hospital, and Fujian Key Laboratory of Molecular Neurology, Fujian Medical University, Fuzhou, Fujian 350001, China.
  • Bu G; Fujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, Institute of Neuroscience, College of Medicine, Xiamen University, Xiamen, Fujian 361102, China; Department of Neuroscience, Mayo Clinic, Jacksonville, FL 32224, USA.
  • An Z; Texas Therapeutics Institute, The Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
  • Huang TY; Neuroscience Initiative, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA.
  • Xu H; Neuroscience Initiative, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA; Fujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, Institute of Neuroscience, College of Medicine, Xiamen University, Xiamen, Fujian 361102, China. Electronic address:
Neuron ; 97(5): 1023-1031.e7, 2018 03 07.
Article em En | MEDLINE | ID: mdl-29518356
ABSTRACT
Mutations in triggering receptor expressed on myeloid cells 2 (TREM2) have been linked to increased Alzheimer's disease (AD) risk. Neurobiological functions of TREM2 and its pathophysiological ligands remain elusive. Here we found that TREM2 directly binds to ß-amyloid (Aß) oligomers with nanomolar affinity, whereas AD-associated TREM2 mutations reduce Aß binding. TREM2 deficiency impairs Aß degradation in primary microglial culture and mouse brain. Aß-induced microglial depolarization, K+ inward current induction, cytokine expression and secretion, migration, proliferation, apoptosis, and morphological changes are dependent on TREM2. In addition, TREM2 interaction with its signaling adaptor DAP12 is enhanced by Aß, regulating downstream phosphorylation of SYK and GSK3ß. Our data demonstrate TREM2 as a microglial Aß receptor transducing physiological and AD-related pathological effects associated with Aß.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Encéfalo / Glicoproteínas de Membrana / Receptores Imunológicos / Peptídeos beta-Amiloides / Microglia / Doença de Alzheimer Idioma: En Ano de publicação: 2018 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Encéfalo / Glicoproteínas de Membrana / Receptores Imunológicos / Peptídeos beta-Amiloides / Microglia / Doença de Alzheimer Idioma: En Ano de publicação: 2018 Tipo de documento: Article