Amyloid-β Oligomers May Impair SNARE-Mediated Exocytosis by Direct Binding to Syntaxin 1a.

Title
Amyloid-β Oligomers May Impair SNARE-Mediated Exocytosis by Direct Binding to Syntaxin 1a.
Authors
양유수김재욱김혜윤류나연이세진김영수임혜원Shin, Yeon-Kyun
Keywords
membrane fusion; Alzheimer's disease; SNARE; neurotransmitter release
Issue Date
2015-08
Publisher
Cell Reports
Citation
VOL 12, NO 8, 1244-1251
Abstract
Alzheimer's disease (AD) is closely associated with synaptic dysfunction, and thus current treatments often aim to stimulate neurotransmission to improve cognitive impairment. Whereas the formation of the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex is essential for synaptic transmission, the correlation between SNAREs and AD neuropathology is unknown. Here, we report that intracellular amyloid-beta (A beta) oligomers directly inhibit SNARE-mediated exocytosis by impairing SNARE complex formation. We observe abnormal reduction of SNARE complex levels in the brains of APP/PS1 transgenic (TG) mice compared to age-matched wild-types. We demonstrate that A beta oligomers block SNARE complex assembly through the direct interaction with a target membrane (t)-SNARE syntaxin 1a in vitro. Furthermore, the results of the in vitro single-vesicle content-mixing assay reveal that A beta oligomers inhibit SNARE-mediated fusion pores. Thus, our study identifies a potential molecular mechanism by which intracellular A beta oligomers hamper SNARE-mediated exocytosis, likely leading to AD-associated synaptic dysfunctions.
URI
http://pubs.kist.re.kr/handle/201004/50564
ISSN
22111247
Appears in Collections:
KIST Publication > Article
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