TY  - JOUR
AU  - Zhou, Y
AU  - Zhu, F
AU  - Liu, Y
AU  - Zheng, M
AU  - Wang, Y
AU  - Zhang, D
AU  - Anraku, Y
AU  - Zou, Y
AU  - Li, J
AU  - Wu, H
AU  - Pang, X
AU  - Tao, W
AU  - Shimoni, O
AU  - Bush, A
AU  - Xue, X
AU  - Shi, B
Y2  - 2020/11/17
Y1  - 2020/10/01
SN  - 2375-2548
UR  - http://hdl.handle.net/11343/251684
AB  - Toxic aggregated amyloid-β accumulation is a key pathogenic event in Alzheimer's disease (AD), which derives from amyloid precursor protein (APP) through sequential cleavage by BACE1 (β-site APP cleavage enzyme 1) and γ-secretase. Small interfering RNAs (siRNAs) show great promise for AD therapy by specific silencing of BACE1. However, lack of effective siRNA brain delivery approaches limits this strategy. Here, we developed a glycosylated "triple-interaction" stabilized polymeric siRNA nanomedicine (Gal-NP@siRNA) to target BACE1 in APP/PS1 transgenic AD mouse model. Gal-NP@siRNA exhibits superior blood stability and can efficiently penetrate the blood-brain barrier (BBB) via glycemia-controlled glucose transporter-1 (Glut1)-mediated transport, thereby ensuring that siRNAs decrease BACE1 expression and modify relative pathways. Noticeably, Gal-NP@siBACE1 administration restored the deterioration of cognitive capacity in AD mice without notable side effects. This "Trojan horse" strategy supports the utility of RNA interference therapy in neurodegenerative diseases.
LA  - English
PB  - AMER ASSOC ADVANCEMENT SCIENCE
T1  - Blood-brain barrier-penetrating siRNA nanomedicine for Alzheimer's disease therapy
DO  - 10.1126/sciadv.abc7031
IS  - Science Advances
VL  - 6
IS  - 41
L1  - /bitstream/handle/11343/251684/PMC7546706.pdf?sequence=1&isAllowed=y
ER  -