Blocking tau transmission by biomimetic graphene nanoparticles.
Blocking tau transmission by biomimetic graphene nanoparticles.
复制标题
通过仿生石墨烯纳米颗粒阻断 tau 蛋白传输。
DOI：
10.1039/d3tb00850a
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Wang,Yichun
中科院分区：
文献类型：
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作者：
Zhu,Runyao;Makwana,KamleshM;Zhang,Youwen;Rajewski,BenjaminH;DelValle,JuanR;Wang,Yichun
牛头病是一类神经退行性疾病，导致认知功能障碍、执行功能障碍和运动障碍。tau病的主要病理特征是大脑中由tau蛋白聚集物组成的神经原纤维缠结的存在。此外，tau聚集物可以从神经元扩散到神经元，导致tau病理的传播。尽管已知有许多小分子可以抑制tau聚集并阻断tau细胞间的传递，但由于特异性差和血脑屏障（BBB）渗透性低，将它们用于治疗应用仍然具有挑战性。石墨烯纳米颗粒先前已被证明可以穿透血脑屏障，并且易于功能化以进行靶向递送。此外，这些纳米级仿生粒子可以自组装或与包括蛋白质在内的各种生物分子组装。在本文中，我们发现石墨烯量子点（GQDs）作为石墨烯纳米颗粒，通过抑制单体tau的成纤维化和触发tau细丝的分解来阻断tau原纤维的播散活性。这种行为归因于GQDs与tau的静电和π -π堆叠相互作用。总之，我们的研究表明，具有仿生特性的GQDs可以有效地抑制和分解病理tau聚集体，从而阻断tau的传播，这支持了它们作为tau病潜在治疗方法的未来发展。
Tauopathies are a class of neurodegenerative diseases resulting in cognitive dysfunction, executive dysfunction, and motor disturbance. The primary pathological feature of tauopathies is the presence of neurofibrillary tangles in the brain composed of tau protein aggregates. Moreover, tau aggregates can spread from neuron to neuron and lead to the propagation of tau pathology. Although numerous small molecules are known to inhibit tau aggregation and block tau cell-to-cell transmission, it is still challenging to use them for therapeutic applications due to poor specificity and low blood-brain barrier (BBB) penetration. Graphene nanoparticles were previously demonstrated to penetrate the BBB and are amenable to functionalization for targeted delivery. Moreover, these nanoscale biomimetic particles can self-assemble or assemble with various biomolecules including proteins. In this paper, we show that graphene quantum dots (GQDs), as graphene nanoparticles, block the seeding activity of tau fibrils by inhibiting the fibrillization of monomeric tau and triggering the disaggregation of tau filaments. This behavior is attributed to electrostatic and π–π stacking interactions of GQDs with tau. Overall, our studies indicate that GQDs with biomimetic properties can efficiently inhibit and disassemble pathological tau aggregates, and thus block tau transmission, which supports their future developments as a potential treatment for tauopathies.