Tau-mediated synaptic and neuronal dysfunction in neurodegenerative disease.

Tau-mediated synaptic and neuronal dysfunction in neurodegenerative disease.
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DOI:
10.1016/j.conb.2018.04.027
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发表时间:
2018-08
影响因子:
5.7
通讯作者:
Gan L
Gan L
中科院分区:
医学2区
文献类型:
--
作者:
Tracy TE;Gan L

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大脑中病理性 tau 蛋白的积累与包括阿尔茨海默病在内的 tau 蛋白病中的神经元退化和认知障碍有关。 Tau 虽然主要位于健康神经元的轴突中,但在致病条件下会在神经元的体细胞和树突中积累。 Tau 蛋白存在于阿尔茨海默病神经元的突触前和突触后区室中。新的研究表明,可溶性 tau 蛋白通过在疾病进展的早期阶段、神经元死亡之前改变突触和神经元功能的特性来触发大脑的病理生理学。在这里,我们回顾了目前对 tau 介导的突触和神经元功能障碍如何导致认知能力下降的理解。描述致病性 tau 蛋白改变突触、树突和轴突的机制将有助于为恢复 tau 蛋白病神经元功能的新策略奠定基础。
The accumulation of pathological tau in the brain is associated with neuronal deterioration and cognitive impairments in tauopathies including Alzheimer’s disease. Tau, while primarily localized in axons of healthy neurons, accumulates in the soma and dendrites of neurons under pathogenic conditions. Tau is found in both presynaptic and postsynaptic compartments of neurons in Alzheimer’s disease. New research supports that soluble forms of tau trigger pathophysiology in the brain by altering properties of synaptic and neuronal function at the early stages of disease progression, before neurons die. Here we review current understanding of how tau-mediated synaptic and neuronal dysfunction contributes to cognitive decline. Delineating the mechanisms by which pathogenic tau alters synapses, dendrites and axons will help lay the foundation for new strategies to restore neuronal function in tauopathy.
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