FcγRIIb mediates amyloid-β neurotoxicity and memory impairment in Alzheimer's disease

Title
FcγRIIb mediates amyloid-β neurotoxicity and memory impairment in Alzheimer's disease
Authors
감태인송성민권영대박혜진ji-Jing Yan임이삭최지우최태용김정연송동근Toshiyuki Takai김용철김기선최세영최석우William L. KleinJunying Yuan정용근
Keywords
amyloid beta neurotoxicity; Fcgamma receptor IIb; memory impairment; Alzheimer's disease; amloid beta receptor
Issue Date
2013-07
Publisher
The Journal of clinical investigation
Citation
VOL 123, NO 7, 2791-2802
Abstract
Amyloid-β (Aβ) 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 Aβ neurotoxicity and neurodegeneration. We found that FcγRIIb is significantly upregulated in the hippocampus of AD brains and neuronal cells exposed to synthetic Aβ. Neuronal FcγRIIb activated ER stress and caspase-12, and Fcgr2b KO primary neurons were resistant to synthetic Aβ-induced cell death in vitro. Fcgr2b deficiency ameliorated Aβ-induced inhibition of long-term potentiation and inhibited the reduction of synaptic density by naturally secreted Aβ. Moreover, genetic depletion of Fcgr2b rescued memory impairments in an AD mouse model. To determine the mechanism of action of FcγRIIb in Aβ neurotoxicity, we demonstrated that soluble Aβ oligomers interact with FcγRIIb in vitro and in AD brains, and that inhibition of their interaction blocks synthetic Aβ neurotoxicity. We conclude that FcγRIIb has an aberrant, but essential, role in Aβ-mediated neuronal dysfunction.
URI
http://pubs.kist.re.kr/handle/201004/45204
ISSN
00219738
Appears in Collections:
KIST Publication > Article
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