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一种用于阿尔茨海默病中病理性 Tau 特异性清除的 Tau 病相关蛋白向靶性和自噬激活纳米组装体。

A Tauopathy-Homing and Autophagy-Activating Nanoassembly for Specific Clearance of Pathogenic Tau in Alzheimer's Disease.

机构信息

Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, P.R. China.

Hangzhou Institute of Innovative Medicine, Zhejiang University, Hangzhou 310058, P.R. China.

出版信息

ACS Nano. 2021 Mar 23;15(3):5263-5275. doi: 10.1021/acsnano.0c10690. Epub 2021 Mar 8.

Abstract

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.

摘要

过度磷酸化和聚集的 tau 积累是包括阿尔茨海默病(AD)在内的 tau 病的一个重要病理标志物,与神经元细胞中的自噬缺陷密切相关。在许多研究中,激活自噬的策略显示出对 AD 的治疗潜力;然而,由于缺乏对病变细胞的选择性,其疗效低和严重的副作用限制了其进一步发展。在这里,我们报告了一种具有 AD 治疗作用的 tau 病归巢纳米组装体(THN)。具体来说,THN 可以与过度磷酸化和/或聚集的 tau 结合,并选择性地在发生 tau 病的细胞中积累。THN 通过刺激自噬流进一步促进致病性 tau 积累的清除,从而挽救 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策略,用于 tau 病归巢和自噬介导的 AD 中致病性 tau 的特异性清除。

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