| First Author | Yang Y | Year | 2015 |
| Journal | Cell Rep | Volume | 12 |
| Issue | 8 | Pages | 1244-51 |
| PubMed ID | 26279571 | Mgi Jnum | J:277592 |
| Mgi Id | MGI:6274100 | Doi | 10.1016/j.celrep.2015.07.044 |
| Citation | Yang Y, et al. (2015) Amyloid-beta Oligomers May Impair SNARE-Mediated Exocytosis by Direct Binding to Syntaxin 1a. Cell Rep 12(8):1244-51 |
| abstractText | 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 (Abeta) 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 Abeta 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 Abeta oligomers inhibit SNARE-mediated fusion pores. Thus, our study identifies a potential molecular mechanism by which intracellular Abeta oligomers hamper SNARE-mediated exocytosis, likely leading to AD-associated synaptic dysfunctions. |
