Dynamic presenilin 1 and synaptotagmin 1 interaction modulates exocytosis and amyloid β production

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• 作者：Katarzyna Marta Zoltowska ; Masato Maesako ; Iryna Lushnikova…
• 关键词：Presenilin 1 ; Synaptotagmin 1 ; Synapse ; Exocytosis ; Amyloid β ; Alzheimer’s disease
• 刊名：Molecular Neurodegeneration
• 出版年：2017
• 出版时间：December 2017
• 年：2017
• 卷：12
• 期：1
• 全文大小：5261KB
• 刊物主题：Neurosciences; Neurology; Molecular Medicine;
• 出版者：BioMed Central
• ISSN：1750-1326
• 卷排序：12

文摘

BackgroundAlzheimer’s disease (AD)-linked protein, presenilin 1 (PS1), is present at the synapse, and the knock-out of presenilin in mice leads to synaptic dysfunction. On the other hand, synaptic activity was shown to influence PS1-dependent generation of distinct amyloid β (Aβ) species. However, the precise nature of these regulations remains unclear. The current study reveals novel role of PS1 at the synapse, and deciphers how PS1 and synaptic vesicle-associated protein, synaptotagmin 1 (Syt1) modulate each other functions in neurons via direct activity-triggered interaction. Additionally, the therapeutic potential of fostering PS1-Syt1 binding is investigated as a synapse-specific strategy for AD prevention.