Yang, Yoosoo Kim, Jaewook Kim, Hye Yun Ryoo, Nayeon Lee, Sejin Kim, YoungSoo Rhim, Hyewhon Shin, Yeon-Kyun 2024-01-20T06:31:06Z 2024-01-20T06:31:06Z 2021-09-05 2015-08-25 2211-1247 https://pubs.kist.re.kr/handle/201004/125112 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. English CELL PRESS TRANSGENIC MOUSE MODELS ALZHEIMERS-DISEASE MEMBRANE-FUSION SYNAPTIC PLASTICITY IN-VITRO NEUROTRANSMITTER RELEASE ACETYLCHOLINE-RELEASE VESICLE DOCKING PROTEIN PEPTIDE Amyloid-beta Oligomers May Impair SNARE-Mediated Exocytosis by Direct Binding to Syntaxin 1a Article 10.1016/j.celrep.2015.07.044 1 CELL REPORTS, v.12, no.8, pp.1244 - 1251 CELL REPORTS 12 8 1244 1251 scie scopus 000360182200004 2-s2.0-84939802655 Cell Biology Cell Biology Article TRANSGENIC MOUSE MODELS ALZHEIMERS-DISEASE MEMBRANE-FUSION SYNAPTIC PLASTICITY IN-VITRO NEUROTRANSMITTER RELEASE ACETYLCHOLINE-RELEASE VESICLE DOCKING PROTEIN PEPTIDE membrane fusion Alzheimer&apos s disease SNARE neurotransmitter release