The shape effect of reconstituted high-density lipoprotein nanocarriers on brain delivery and Aβ clearance

Song, Huahua; Ma, Xinyi; Xu, Jianrong; Song, Qing; Meng, Hu; Gu, Xiao; Zhang, Qian; Hou, Liang; Chen, Lepei; Huang, Yukun; Yu, Ping; Wang, Dayuan; Jiang, Gan; Huang, Meng; Chen, Hongzhuan; Gao, Xiaoling

doi:10.1007/s12274-018-2107-8

Cited by 7 publications

(3 citation statements)

References 53 publications

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“…These effects were amplified by adding Mangostin, a model drug that accelerates Aβ degradation, to apoE containing HDL-P, and demonstrated enhanced degradation of Aβ and improved memory deficits ( Song et al, 2016 ). In a more recent study, Song et al (2018) examined the effects of rHDL’s shape on its brain delivery, Aβ degradation, and anti-AD efficacy by comparing 27 nm spherical and discoidal apoE3-NPs nanocarriers. Spherical NPs, relative to discoidal particles, exerted the best effect due to superior brain distribution after intravenous administration, powerfully reduced Aβ deposition, decreased microglia activation, attenuated neurological damage, and rescued memory deficits in the same aging model.…”

Section: Introductionmentioning

confidence: 99%

Understanding the Exchange of Systemic HDL Particles Into the Brain and Vascular Cells Has Diagnostic and Therapeutic Implications for Neurodegenerative Diseases

et al. 2021

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High-density lipoproteins (HDLs) are complex, heterogenous lipoprotein particles, consisting of a large family of apolipoproteins, formed in subspecies of distinct shapes, sizes, and functions and are synthesized in both the brain and the periphery. HDL apolipoproteins are important determinants of Alzheimer’s disease (AD) pathology and vascular dementia, having both central and peripheral effects on brain amyloid-beta (Aβ) accumulation and vascular functions, however, the extent to which HDL particles (HLD-P) can exchange their protein and lipid components between the central nervous system (CNS) and the systemic circulation remains unclear. In this review, we delineate how HDL’s structure and composition enable exchange between the brain, cerebrospinal fluid (CSF) compartment, and vascular cells that ultimately affect brain amyloid metabolism and atherosclerosis. Accordingly, we then elucidate how modifications of HDL-P have diagnostic and therapeutic potential for brain vascular and neurodegenerative diseases.

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Section: Introductionmentioning

confidence: 99%

Understanding the Exchange of Systemic HDL Particles Into the Brain and Vascular Cells Has Diagnostic and Therapeutic Implications for Neurodegenerative Diseases

et al. 2021

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“…As a result, reconstitution of membrane proteins using membrane mimetics such as bicelles, micelles, liposomes, or nanodiscs has significantly eased the interrogation of membrane-associated proteins. Particularly, there is considerable interest in the development and application of nanodiscs. , Use of nanodiscs as a potential chemical tool for protein misfolded diseases like Alzheimer’s disease is bound to create avenues for exciting biomedical applications. , These nanodiscs provide a detergent-free native-like lipid bilayer environment for functional reconstitution of a membrane protein or protein–protein complex. In addition, the size-tunable and lipid selectivity properties of nanodiscs have enabled researchers to design membrane protein selective nanodiscs for structural and functional studies …”

Section: Introductionmentioning

confidence: 99%

Self-Assembly of Polymer-Encased Lipid Nanodiscs and Membrane Protein Reconstitution

Sahoo¹,

Genjo²,

Moharana

et al. 2019

J. Phys. Chem. B

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The absence of detergent and curvature makes nanodiscs excellent membrane mimetics. The lack of structural and mechanistic model of polymer-encapsulated lipid nanodiscs limits their use in the study of the structure, dynamics, and functions of membrane proteins. In this study, we parameterized and optimized the coarse-graining (CG) bead mapping for two differently charged and functionalized copolymers, containing styrene–maleic acid (SMAEA) and polymethacrylate (PMAQA), for the Martini force-field framework and showed nanodisc formation (<8 nm diameter) on a time scale of tens of microseconds using molecular dynamics (MD) simulations. Structural models of ∼2.0 or 4.8 kDa PMAQA and ∼2.2 kDa SMAEA polymer-based lipid nanodiscs highlight the importance of the polymer chemical structure, size, and polymer–lipid ratio in the optimization of the nanodisc structure. The ideal spatial arrangement of polymers in nanodiscs, nanodisc size, and thermal stability obtained from our MD simulation correlates well with the experimental observations. The polymer–nanodiscs were tested for the reconstitution of single-pass or multipass transmembrane proteins. We expect this study to be useful in the development of novel polymer-based lipid nanodiscs and for the structural studies of membrane proteins.

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“…Nance and coworkers show that curcumin-loaded polymeric NPs exhibit a considerable neuroprotective effect in a hypoxic-ischemic brain injury rat model [35]. Gao and coworkers study on the shape effect of E3-reconstituted high-density lipoprotein (rHDL) on the brain delivery, and demonstrate that spherical rHDL exhibits better capabilities in reducing Aβ deposition and rescuing memory deficits in a mouse model of Alzheimer's disease [36]. Chung and coworkers describe a kidney-targeting peptide-modified multimodal micelle as a potential drug nanocarrier for kidney diseases [37].…”

mentioning

confidence: 99%

The inaugural Nano Research Young Innovators (NR45) Award in nanobiotechnology

Dai

2018

Nano Res.

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The shape effect of reconstituted high-density lipoprotein nanocarriers on brain delivery and Aβ clearance

Cited by 7 publications

References 53 publications

Understanding the Exchange of Systemic HDL Particles Into the Brain and Vascular Cells Has Diagnostic and Therapeutic Implications for Neurodegenerative Diseases

Understanding the Exchange of Systemic HDL Particles Into the Brain and Vascular Cells Has Diagnostic and Therapeutic Implications for Neurodegenerative Diseases

Self-Assembly of Polymer-Encased Lipid Nanodiscs and Membrane Protein Reconstitution

The inaugural Nano Research Young Innovators (NR45) Award in nanobiotechnology

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