@article{401f7ed9515341c49b8d771fdaf62f3c,
title = "A Self-Assembled α-Synuclein Nanoscavenger for Parkinson's Disease",
abstract = "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 via a 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.",
keywords = "autophagy, curcumin analogue, exosome secretion, intranasal administration, Parkinson's disease, TFEB, α-synuclein",
author = "Jingyi Liu and Chao Liu and Jinfeng Zhang and Yunming Zhang and Keyin Liu and Song, {Ju Xian} and Sreenivasmurthy, {Sravan Gopalkrishnashetty} and Ziying Wang and Yesi Shi and Chengchao Chu and Yang Zhang and Caisheng Wu and Xianhua Deng and Xingyang Liu and Jing Song and Rongqiang Zhuang and Shuqiong Huang and Pengfei Zhang and Min Li and Lei Wen and Zhang, {Yun wu} and Gang Liu",
note = "Funding Information: The work was supported by the National Key Research and Development Program of China (2017YFA0205201, 2016YFC1305903 and 2018YFC2000400), the National Natural Science Foundation of China (81422023, 81925019, 81603015, 81774377, 81373999, 81771377, U1705281 U1705285, and U1505221), the Fundamental Research Funds for the Central Universities (20720190088 and 20720180049), the Program for New Century Excellent Talents in University, China (NCET-13-0502 and NCET-13-0505) the Natural Science Foundation of Fujian Province of China (Grant No. 2018J05144), and the International Postdoctoral Exchange Fellowship Programs (to J.L.). All animal experiments were approved by the Animal Management and Ethics Committee of Xiamen University. Funding Information: The work was supported by the National Key Research and Development Program of China (2017YFA0205201, 2016YFC1305903, and 2018YFC2000400), the National Natural Science Foundation of China (81422023, 81925019, 81603015, 81774377, 81373999, 81771377, U1705281, U1705285, and U1505221), the Fundamental Research Funds for the Central Universities (20720190088 and 20720180049), the Program for New Century Excellent Talents in University, China (NCET-13-0502 and NCET-13-0505), the Natural Science Foundation of Fujian Province of China (Grant No. 2018J05144), and the International Postdoctoral Exchange Fellowship Programs (to J.L.). All animal experiments were approved by the Animal Management and Ethics Committee of Xiamen University.",
year = "2020",
month = feb,
day = "25",
doi = "10.1021/acsnano.9b06453",
language = "English",
volume = "14",
pages = "1533--1549",
journal = "ACS Nano",
issn = "1936-0851",
publisher = "American Chemical Society",
number = "2",
}