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

Yoosoo Yang, Jaewook Kim, Hye Yun Kim, Nayeon Ryoo, Sejin Lee, Young Soo Kim, Hyewhon Rhim, Yeon Kyun Shin

Research output: Contribution to journalArticle

19 Citations (Scopus)

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-β (Aβ) 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 Aβ 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 Aβ oligomers inhibit SNARE-mediated fusion pores. Thus, our study identifies a potential molecular mechanism by which intracellular Aβ oligomers hamper SNARE-mediated exocytosis, likely leading to AD-associated synaptic dysfunctions.

Original languageEnglish
Article number1940
Pages (from-to)1244-1251
Number of pages8
JournalCell Reports
Volume12
Issue number8
DOIs
Publication statusPublished - 2015 Aug 25

Fingerprint

Syntaxin 1
Exocytosis
Oligomers
Amyloid
SNARE Proteins
Alzheimer Disease
Proteins
Synaptic Transmission
Transgenic Mice
Assays
Brain
Fusion reactions
Membranes

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Yang, Yoosoo ; Kim, Jaewook ; Kim, Hye Yun ; Ryoo, Nayeon ; Lee, Sejin ; Kim, Young Soo ; Rhim, Hyewhon ; Shin, Yeon Kyun. / Amyloid-β Oligomers May Impair SNARE-Mediated Exocytosis by Direct Binding to Syntaxin 1a. In: Cell Reports. 2015 ; Vol. 12, No. 8. pp. 1244-1251.
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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-β (Aβ) 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 Aβ 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 Aβ oligomers inhibit SNARE-mediated fusion pores. Thus, our study identifies a potential molecular mechanism by which intracellular Aβ oligomers hamper SNARE-mediated exocytosis, likely leading to AD-associated synaptic dysfunctions.",
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Yang, Y, Kim, J, Kim, HY, Ryoo, N, Lee, S, Kim, YS, Rhim, H & Shin, YK 2015, 'Amyloid-β Oligomers May Impair SNARE-Mediated Exocytosis by Direct Binding to Syntaxin 1a', Cell Reports, vol. 12, no. 8, 1940, pp. 1244-1251. https://doi.org/10.1016/j.celrep.2015.07.044

Amyloid-β Oligomers May Impair SNARE-Mediated Exocytosis by Direct Binding to Syntaxin 1a. / Yang, Yoosoo; Kim, Jaewook; Kim, Hye Yun; Ryoo, Nayeon; Lee, Sejin; Kim, Young Soo; Rhim, Hyewhon; Shin, Yeon Kyun.

In: Cell Reports, Vol. 12, No. 8, 1940, 25.08.2015, p. 1244-1251.

Research output: Contribution to journalArticle

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AU - Yang, Yoosoo

AU - Kim, Jaewook

AU - Kim, Hye Yun

AU - Ryoo, Nayeon

AU - Lee, Sejin

AU - Kim, Young Soo

AU - Rhim, Hyewhon

AU - Shin, Yeon Kyun

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