RGD Reference Report - Fc¿RIIb mediates amyloid-ß neurotoxicity and memory impairment in Alzheimer's disease. - Rat Genome Database

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Fc¿RIIb mediates amyloid-ß neurotoxicity and memory impairment in Alzheimer's disease.

Authors: Kam, Tae-In  Song, Sungmin  Gwon, Youngdae  Park, Hyejin  Yan, Ji-Jing  Im, Isak  Choi, Ji-Woo  Choi, Tae-Yong  Kim, Jeongyeon  Song, Dong-Keun  Takai, Toshiyuki  Kim, Yong-Chul  Kim, Key-Sun  Choi, Se-Young  Choi, Sukwoo  Klein, William L  Yuan, Junying  Jung, Yong-Keun 
Citation: Kam TI, etal., J Clin Invest. 2013 Jul;123(7):2791-802. doi: 10.1172/JCI66827. Epub 2013 Jun 10.
RGD ID: 12910988
Pubmed: PMID:23921129   (View Abstract at PubMed)
PMCID: PMC3696552   (View Article at PubMed Central)
DOI: DOI:10.1172/JCI66827   (Journal Full-text)

Amyloid-ß (Aß) induces neuronal loss and cognitive deficits and is believed to be a prominent cause of Alzheimer's disease (AD); however, the cellular pathology of the disease is not fully understood. Here, we report that IgG Fcγ receptor II-b (FcγRIIb) mediates Aß neurotoxicity and neurodegeneration. We found that FcγRIIb is significantly upregulated in the hippocampus of AD brains and neuronal cells exposed to synthetic Aß. Neuronal FcγRIIb activated ER stress and caspase-12, and Fcgr2b KO primary neurons were resistant to synthetic Aß-induced cell death in vitro. Fcgr2b deficiency ameliorated Aß-induced inhibition of long-term potentiation and inhibited the reduction of synaptic density by naturally secreted Aß. Moreover, genetic depletion of Fcgr2b rescued memory impairments in an AD mouse model. To determine the mechanism of action of FcγRIIb in Aß neurotoxicity, we demonstrated that soluble Aß oligomers interact with FcγRIIb in vitro and in AD brains, and that inhibition of their interaction blocks synthetic Aß neurotoxicity. We conclude that FcγRIIb has an aberrant, but essential, role in Aß-mediated neuronal dysfunction.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

Objects Annotated

Genes (Rattus norvegicus)
Fcgr2b  (Fc gamma receptor 2B)


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