| Autor: |
Liu, Jingyi, Liu, Chao, Zhang, Jinfeng, Zhang, Yunming, Liu, Keyin, Song, Ju-Xian, Sreenivasmurthy, Sravan Gopalkrishnashetty, Wang, Ziying, Shi, Yesi, Chu, Chengchao, Zhang, Yang, Wu, Caisheng, Deng, Xianhua, Liu, Xingyang, Song, Jing, Zhuang, Rongqiang, Huang, Shuqiong, Zhang, Pengfei, Li, Min, Wen, Lei, Zhang, Yun wu, Liu, Gang |
| Zdroj: |
ACS Nano; February 2020, Vol. 14 Issue: 2 p1533-1549, 17p |
| Abstrakt: |
Although emerging evidence suggests that the pathogenesis of Parkinson’s disease (PD) is closely related to the aggregation of alpha-synuclein (α-syn) in the midbrain, the clearance of α-syn remains an unmet clinical need. Here, we develop a simple and efficient strategy for fabricating the α-syn nanoscavenger for PD viaa reprecipitation self-assembly procedure. The curcumin analogue-based nanoscavenger (NanoCA) is engineered to be capable of a controlled-release property to stimulate nuclear translocation of the major autophagy regulator, transcription factor EB (TFEB), triggering both autophagy and calcium-dependent exosome secretion for the clearance of α-syn. Pretreatment of NanoCA protects cell lines and primary neurons from MPP+-induced neurotoxicity. More importantly, a rapid arousal intranasal delivery system (RA-IDDS) was designed and applied for the brain-targeted delivery of NanoCA, which affords robust neuroprotection against behavioral deficits and promotes clearance of monomer, oligomer, and aggregates of α-syn in the midbrain of an MPTP mouse model of PD. Our findings provide a clinically translatable therapeutic strategy aimed at neuroprotection and disease modification in PD. |
| Databáze: |
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