Adult Stem Cell Research Center, College of Veterinary Medicine, Seoul National University, Seoul 08826, Korea.
Research Institute for Veterinary Science, College of Veterinary Medicine, Seoul National University, Seoul 08826, Korea.
Nano Lett. 2021 Mar 10;21(5):2339-2346. doi: 10.1021/acs.nanolett.0c03741. Epub 2021 Jan 20.
While the neuropathological characteristics of Niemann-Pick disease type C (NPC) result in a fatal diagnosis, the development of clinically available therapeutic agent remains a challenge. Here we propose graphene quantum dots (GQDs) as a potential candidate for the impaired functions in NPC in vivo. In addition to the previous findings that GQDs exhibit negligible long-term toxicity and are capable of penetrating the blood-brain barrier, GQD treatment reduces the aggregation of cholesterol in the lysosome through expressed physical interactions. GQDs also promote autophagy and restore defective autophagic flux, which, in turn, decreases the atypical accumulation of autophagic vacuoles. More importantly, the injection of GQDs inhibits the loss of Purkinje cells in the cerebellum while also demonstrating reduced activation of microglia. The ability of GQDs to alleviate impaired functions in NPC proves the promise and potential of the use of GQDs toward resolving NPC and other related disorders.
虽然尼曼-匹克病 C 型（NPC）的神经病理学特征导致了致命的诊断，但开发临床可用的治疗药物仍然是一个挑战。在这里，我们提出石墨烯量子点（GQDs）作为 NPC 体内功能障碍的潜在候选药物。除了先前发现的 GQDs 表现出可忽略的长期毒性并且能够穿透血脑屏障之外，GQD 治疗还通过表达的物理相互作用减少了溶酶体中胆固醇的聚集。GQDs 还促进自噬并恢复有缺陷的自噬流，这反过来又减少了自噬空泡的异常积累。更重要的是，GQD 的注射抑制了小脑浦肯野细胞的丢失，同时也显示出小胶质细胞的激活减少。GQDs 缓解 NPC 功能障碍的能力证明了 GQDs 在解决 NPC 和其他相关疾病方面的应用具有很大的希望和潜力。
