Biomimetic Nanocarrier Targeting Drug(s) to Upstream-Receptor Mechanisms in Dementia: Focusing on Linking Pathogenic Cascades

D'Arrigo, Joseph

doi:10.3390/biomimetics5010011

Cited by 12 publications

(15 citation statements)

References 62 publications

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“…Among the latter, diseases of the central nervous system are of special interest because of the tightness of the BBB. As HDL-like nanoparticles can be artificially reconstituted, a better understanding of transendothelial HDL transport also opens avenues towards improved delivery of tracers and drugs into various tissues for diagnostics and therapy, respectively [ 185 , 186 , 187 , 188 ].…”

Section: Discussionmentioning

confidence: 99%

The Endothelium Is Both a Target and a Barrier of HDL’s Protective Functions

Robert

Osto

Eckardstein

2021

Cells

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The vascular endothelium serves as a barrier between the intravascular and extravascular compartments. High-density lipoproteins (HDL) have two kinds of interactions with this barrier. First, bloodborne HDL must pass the endothelium to access extravascular tissues, for example the arterial wall or the brain, to mediate cholesterol efflux from macrophages and other cells or exert other functions. To complete reverse cholesterol transport, HDL must even pass the endothelium a second time to re-enter circulation via the lymphatics. Transendothelial HDL transport is a regulated process involving scavenger receptor SR-BI, endothelial lipase, and ATP binding cassette transporters A1 and G1. Second, HDL helps to maintain the integrity of the endothelial barrier by (i) promoting junction closure as well as (ii) repair by stimulating the proliferation and migration of endothelial cells and their progenitor cells, and by preventing (iii) loss of glycocalix, (iv) apoptosis, as well as (v) transmigration of inflammatory cells. Additional vasoprotective functions of HDL include (vi) the induction of nitric oxide (NO) production and (vii) the inhibition of reactive oxygen species (ROS) production. These vasoprotective functions are exerted by the interactions of HDL particles with SR-BI as well as specific agonists carried by HDL, notably sphingosine-1-phophate (S1P), with their specific cellular counterparts, e.g., S1P receptors. Various diseases modify the protein and lipid composition and thereby the endothelial functionality of HDL. Thorough understanding of the structure–function relationships underlying the multiple interactions of HDL with endothelial cells is expected to elucidate new targets and strategies for the treatment or prevention of various diseases.

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Section: Discussionmentioning

confidence: 99%

The Endothelium Is Both a Target and a Barrier of HDL’s Protective Functions

Robert

Osto

Eckardstein

2021

Cells

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“…Based on the described SAA role in AD, a potential effective therapeutic approach could target the SAA receptor promoting the SAA cell internalization and thus its proinflammatory activity [ 83 ]. In this regard, a nanoparticle-based approach targeting SR-BI, the scavenger receptor for HDLs, has been proposed by some authors to counteract SAA's deleterious effects [ 84 ]. Another suggestion for a potential therapeutic strategy comes from in vitro evidence.…”

Section: Serum Amyloid a (Saa)mentioning

confidence: 99%

Connection between the Altered HDL Antioxidant and Anti‐Inflammatory Properties and the Risk to Develop Alzheimer’s Disease: A Narrative Review

Zimetti

Adorni

Marsillach

et al. 2021

Oxidative Medicine and Cellular Longevity

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The protein composition of high-density lipoprotein (HDL) is extremely fluid. The quantity and quality of protein constituents drive the multiple biological functions of these lipoproteins, which include the ability to contrast atherogenesis, sustained inflammation, and toxic effects of reactive species. Several diseases where inflammation and oxidative stress participate in the pathogenetic process are characterized by perturbation in the HDL proteome. This change inevitably affects the functionality of the lipoprotein. An enlightening example in this frame comes from the literature on Alzheimer’s disease (AD). Growing lines of epidemiological evidence suggest that loss of HDL-associated proteins, such as lipoprotein phospholipase A2 (Lp-PLA2), glutathione peroxidase-3 (GPx-3), and paraoxonase-1 and paraoxonase-3 (PON1, PON3), may be a feature of AD, even at the early stage. Moreover, the decrease in these enzymes with antioxidant/defensive action appears to be accompanied by a parallel increase of prooxidant and proinflammatory mediators, in particular myeloperoxidase (MPO) and serum amyloid A (SAA). This type of derangement of balance between two opposite forces makes HDL dysfunctional, i.e., unable to exert its “natural” vasculoprotective property. In this review, we summarized and critically analyzed the most significant findings linking HDL accessory proteins and AD. We also discuss the most convincing hypothesis explaining the mechanism by which an observed systemic occurrence may have repercussions in the brain.

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“…Meanwhile, much evidence indicates a protective (i.e., ordinarily anti-inflammatory) role for HDL, and its major apolipoprotein (apoA-1), in Alzheimer's disease (e.g., [5,11,[18][19][20]) (cf. [21]).…”

Section: Covid-19 ("Hdl-like") Lcm/nd Nanoemulsion and (Late-onset) Dementiamentioning

confidence: 99%

Biobased Nanoemulsion for Blocking Covid-19 From Accelerating Alzheimer's Disease

D'Arrigo

2021

Juvenis scientia

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An effective therapeutic strategy to delay dementia could be based upon nanotargeting drug(s), using lipid nanocarriers (i.e., biobased nanoemulsion technology), toward a major serum amyloid A (SAA) receptor responsible for certain proinflammatory, SAA-mediated, cell signaling events. For example, other investigators have already confirmed that SR-BI receptors (or its human ortholog CLA-1) function as proinflammatory cell-surface SAA receptors, and additionally report that various ligands for CLA-1/SR-BI "efficiently compete" with SAA for CLA-1/SR-BI binding. A similar benefit (of "competitive binding") may well accompany the clinical intravenous use of the ("HDL-like") lipid nanocarriers (i.e., biobased nanoemulsion [see above]), which have already been repeatedly described in the peer-reviewed literature as a targeted (and SR-BI mediated) drug-delivery agent. To conclude, the above-proposed "competitive binding", between SAA and such biobased nanoemulsion(s), could assist/enhance the protective (ordinarily anti-inflammatory) role of HDL - as well as provide targeted drug-delivery to the (human) brain cells bearing CLA-1/SR-BI receptors. The first resulting advantage is that this (intravenous) colloidal-nanocarrier therapeutic makes it possible for various cell types, all potentially implicated in Alzheimer's disease and/or (late-onset) dementia, to be simultaneously sought out and better reached for localized drug treatment of brain tissue in vivo. A second major advantage is that this therapeutic-target approach has particular relevance to the current COVID-19 human pandemic; namely, immune response and excessive inflammation in COVID-19 infection may accelerate the progression of brain inflammatory neurodegeneration which, if effectively halted, might play a major role in reducing Alzheimer's disease pathology.

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Biomimetic Nanocarrier Targeting Drug(s) to Upstream-Receptor Mechanisms in Dementia: Focusing on Linking Pathogenic Cascades

Cited by 12 publications

References 62 publications

The Endothelium Is Both a Target and a Barrier of HDL’s Protective Functions

The Endothelium Is Both a Target and a Barrier of HDL’s Protective Functions

Connection between the Altered HDL Antioxidant and Anti‐Inflammatory Properties and the Risk to Develop Alzheimer’s Disease: A Narrative Review

Biobased Nanoemulsion for Blocking Covid-19 From Accelerating Alzheimer's Disease

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