Multifunctional Nanostructure RAP‐RL Rescues Alzheimer's Cognitive Deficits through Remodeling the Neurovascular Unit. Issue 2 (10th December 2020)

• Record Type: Journal Article
• Authors: Zhang, Qian; Song, Qingxiang; Gu, Xiao; Zheng, Mengna; Wang, Antian; Jiang, Gan; Huang, Meng; Chen, Huan; Qiu, Yu; Bo, Bin; Tong, Shanbao; Shao, Rong; Li, Binyin; Wang, Gang; Wang, Hao; Hu, Yongbo; Chen, Hongzhuan; Gao, Xiaoling
• Is Part Of: Advanced science. Volume 8:Issue 2(2021)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2020-12-10
• Subjects: Alzheimer's disease -- cerebrovasculature -- multifunctional nanostructure -- NVU remodeling; Science -- Periodicals; 505
• DOI: 10.1002/advs.202001918
• Languages: English
• ISSNs: 2198-3844

Abstract

Abstract: Cerebrovascular dysfunction characterized by the neurovascular unit (NVU) impairment contributes to the pathogenesis of Alzheimer's disease (AD). In this study, a cerebrovascular‐targeting multifunctional lipoprotein‐biomimetic nanostructure (RAP‐RL) constituted with an antagonist peptide (RAP) of receptor for advanced glycation end‐products (RAGE), monosialotetrahexosyl ganglioside, and apolipoprotein E3 is developed to recover the functional NVU and normalize the cerebral vasculature. RAP‐RL accumulates along the cerebral microvasculature through the specific binding of RAP to RAGE, which is overexpressed on cerebral endothelial cells in AD. It effectively accelerates the clearance of perivascular A β, normalizes the morphology and functions of cerebrovasculature, and restores the structural integrity and functions of NVU. RAP‐RL markedly rescues the spatial learning and memory in APP/PS1 mice. Collectively, this study demonstrates the potential of the multifunctional nanostructure RAP‐RL as a disease‐modifying modality for AD treatment and provides the proof of concept that remodeling the functional NVU may represent a promising therapeutic approach toward effective intervention of AD. Abstract : RAP‐RL, a multifunctional lipoprotein‐like nanostructure, which contains RAGE antagonist peptide (RAP), GM1 and ApoE3, is designed to rescue AD cognitive deficits through remodeling the neurovascular unit. RAP‐RL accumulates along the cerebral microvasculature through the specific binding of RAP to RAGE. It decreases neuroinflammation, accelerates the perivascular Aβ clearance, restores the structure and function of the cerebrovasculature system, and efficiently alleviates spatial learning and memory in AD model mice.