A Nanocleaner Specifically Penetrates The Blood‒Brain Barrier At Lesions To Clean Toxic Proteins And Regulate Inflammation In Alzheimer's Disease
https://doi.org/10.1016/j.apsb.2021.04.022
In this new article publication from Acta Pharmaceutica Sinica B , authors Ting Lei, Zhihang Yang, Xue Xia, Yuxiu Chen, Xiaotong Yang, Rou Xie, Fan Tong, Xiaolin Wang, Huile Gao from Sichuan University, Chengdu, China and Macau University of Science and Technology, Macau, China discuss how nanocleaners can specifically penetrate the blood‒brain barrier at lesions to clean toxic proteins and regulate inflammation in Alzheimer's disease.
Insurmountable blood‒brain barrier (BBB) and complex pathological features are the key factors affecting the treatment of Alzheimer's disease (AD). Poor accumulation of drugs in lesion sites and undesired effectiveness of simply reducing A β deposition or TAU protein need to be resolved urgently.
The authors of this paper designed a nanocleaner with a rapamycin-loaded ROS-responsive PLGA core and surface modification with KLVFF peptide and acid-cleavable DAG peptide [R@(ox-PLGA)-KcD]. DAG can enhance the targeting and internalization effect of nanocleaner towards neurovascular unit endothelial cells in AD lesions, and subsequently detach from nanocleaner in response to acidic microenvironment of endosomes to promote the transcytosis of nanocleaner from endothelial cells into brain parenchyma. Then exposed KLVFF can capture and carry A β to microglia, attenuating A β -induced neurotoxicity. Rapamycin, an autophagy promoter, is rapidly liberated from the nanocleaner in the high ROS level of lesions to improve A β degradation and normalize inflammatory condition. This design altogether accelerates A β degradation and alleviates oxidative stress and excessive inflammatory response.
Collectively, the findings of this paper offer a strategy to target AD lesions precisely and multi-pronged therapies for clearing the toxic proteins and modulating lesion microenvironment, to achieve efficient AD therapy.
Article reference: Ting Lei, Zhihang Yang, Xue Xia, Yuxiu Chen, Xiaotong Yang, Rou Xie, Fan Tong, Xiaolin Wang, Huile Gao, A nanocleaner specifically penetrates the blood‒brain barrier at lesions to clean toxic proteins and regulate inflammation in Alzheimer's disease, Acta Pharmaceutica Sinica B, Volume 11, Issue 12, 2021, Pages 4032-4044, ISSN 2211-3835, https://doi.org/10.1016/j.apsb.2021.04.022 .
Keywords: Alzheimer's disease, A β -capturing, Autophagy, ROS-responsive, Anti-inflammatory, Blood‒brain barrier transcytosis, Microenvironment modulation, Lesion targeting
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CiteScore: 12.5
Impact Factor: 11.614
JIF without self-citation: 10.746
ISSN 2211-3835
Acta Pharmaceutica Sinica B