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首页> 外文期刊>Neuron >Synaptogyrin-3 Mediates Presynaptic Dysfunction Induced by Tau
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Synaptogyrin-3 Mediates Presynaptic Dysfunction Induced by Tau

机译:Synaptogyrin-3介导Tau引起的突触前功能障碍

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摘要

Synaptic dysfunction is an early pathological feature of neurodegenerative diseases associated with Tau, including Alzheimer's disease. Interfering with early synaptic dysfunction may be therapeutically beneficial to prevent cognitive decline and disease progression, but the mechanisms underlying synaptic defects associated with Tau are unclear. In disease conditions, Tau mislocalizes into pre- and postsynaptic compartments; here we show that, under pathological conditions, Tau binds to presynaptic vesicles in Alzheimer's disease patient brain. We define that the binding of Tau to synaptic vesicles is mediated by the transmembrane vesicle protein Synaptogyrin-3. In fly and mouse models of Tauopathy, reduction of Synaptogyrin-3 prevents the association of presynaptic Tau with vesicles, alleviates Tau-induced defects in vesicle mobility, and restores neurotransmitter release. This work therefore identifies Synaptogyrin-3 as the binding partner of Tau on synaptic vesicles, revealing a new presynapse-specific Tau interactor, which may contribute to early synaptic dysfunction in neurodegenerative diseases associated with Tau.
机译:突触功能障碍是与TAU相关的神经变性疾病的早期病理特征,包括阿尔茨海默病。干扰早期突触功能障碍可能是治疗上有益的,以防止认知下降和疾病进展,但与TAU相关的突触缺陷潜在的机制尚不清楚。在疾病条件下,TAU将误差分为前后隔室;在这里,我们表明,在病理条件下,Tau与阿尔茨海默病患者脑中的突触囊泡结合。我们将Tau与突触囊泡的结合定义由跨膜囊泡蛋白突触吡喃-3介导。在施坦病的飞行和小鼠模型中,Sychaptogyrin-3的减少可防止突触前Tau与囊泡的关联,缓解囊泡迁移率的Tau诱导的缺陷,并恢复神经递质释放。因此,这项工作将SynaptoGyrin-3识别为Tau上的突触囊泡的结合伴侣,揭示了一种新的预先跨越特异性Tau互动者,这可能导致与TAU相关的神经变性疾病的早期突触功能障碍。

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  • 来源
    《Neuron》 |2018年第4期|共21页
  • 作者单位

    VIB KU Leuven Ctr Brain &

    Dis Res B-3000 Leuven Belgium;

    VIB KU Leuven Ctr Brain &

    Dis Res B-3000 Leuven Belgium;

    VIB KU Leuven Ctr Brain &

    Dis Res B-3000 Leuven Belgium;

    VIB KU Leuven Ctr Brain &

    Dis Res B-3000 Leuven Belgium;

    VIB KU Leuven Ctr Brain &

    Dis Res B-3000 Leuven Belgium;

    Catholic Univ Louvain Inst Neurosci Alzheimer Dementia Grp B-1200 Brussels Belgium;

    VIB KU Leuven Ctr Brain &

    Dis Res B-3000 Leuven Belgium;

    VIB UGent Ctr Med Biotechnol B-9000 Ghent Belgium;

    Catholic Univ Louvain Inst Neurosci Alzheimer Dementia Grp B-1200 Brussels Belgium;

    Univ Edinburgh Euan MacDonald Ctr UK Dementia Res Inst Edinburgh EH8 9JZ Midlothian Scotland;

    VIB KU Leuven Ctr Brain &

    Dis Res B-3000 Leuven Belgium;

    VIB KU Leuven Ctr Brain &

    Dis Res B-3000 Leuven Belgium;

    VIB KU Leuven Ctr Brain &

    Dis Res B-3000 Leuven Belgium;

    VIB KU Leuven Ctr Brain &

    Dis Res B-3000 Leuven Belgium;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 神经病学;
  • 关键词

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