A Tauopathy-Homing and Autophagy-Activating Nanoassembly for Specific Clearance of Pathogenic Tau in Alzheimer’s Disease,ACS Nano

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A Tauopathy-Homing and Autophagy-Activating Nanoassembly for Specific Clearance of Pathogenic Tau in Alzheimer’s Disease
ACS Nano ( IF 15.8 ) Pub Date : 2021-03-08 , DOI: 10.1021/acsnano.0c10690
Heng Sun _{1,

2} , Yan Zhong _{3,

4} , Xiandi Zhu _{3,

4} , Hongwei Liao ₁ , Jiyoung Lee ₁ , Ying Chen ₁ , Lijuan Ma _{3,

4} , Jiafeng Ren _{1,

2} , Meng Zhao _{1,

2} , Mengjiao Tu _{3,

4} , Fangyuan Li _{1,

2} , Hong Zhang _{3,

4,

5} , Mei Tian _{3,

4} , Daishun Ling _{1,

2,

5,

6}

Affiliation

The hyperphosphorylated and aggregated tau accumulation represents a significant pathological hallmark of tauopathies including Alzheimer’s disease (AD), which is highly associated with defective autophagy in neuronal cells. Autophagy-activating strategies demonstrate the therapeutic potential for AD in many studies; however, further development is limited by their low efficacy and serious side effects that result from a lack of selectivity for diseased cells. Herein, we report a tauopathy-homing nanoassembly (THN) with autophagy-activating capacity for AD treatment. Specifically, the THN can bind to hyperphosphorylated and/or aggregated tau and selectively accumulate in cells undergoing tauopathy. The THN further promotes the clearance of pathogenic tau accumulation by stimulating autophagic flux, consequently rescuing neuron viability and cognitive functions in AD rats. This study presents a promising nanotechnology-based strategy for tauopathy-homing and autophagy-mediated specific removal of pathogenic tau in AD.

中文翻译：

Tauopathy归巢和自噬激活纳米组件的阿尔茨海默氏病的致病性Tau的特异性清除。

过度磷酸化和聚集的tau积累代表包括Alzheimer病（AD）在内的Tauopathies的重要病理标志，这与神经元细胞中的自噬缺陷有关。自噬激活策略在许多研究中证明了AD的治疗潜力。然而，由于缺乏对患病细胞的选择性，它们的低功效和严重的副作用限制了其进一步的发展。在本文中，我们报道了具有自噬激活能力的AD治疗tauopathy归巢纳米组件（THN）。具体地，THN可结合至高磷酸化和/或聚集的tau，并选择性地积累在经历tau病的细胞中。THN通过刺激自噬通量进一步促进清除病原性tau积累，因此可以挽救AD大鼠的神经元活力和认知功能。这项研究提出了一种有前途的基于纳米技术的战略，用于tauopathy归巢和自噬介导的AD中病原tau的特异性清除。

更新日期：2021-03-23

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