Blood-brain barrier receptors and transporters: an insight on their function and how to exploit them through nanotechnology

Moura, Rui Pedro; Martins, Cláudia; Pinto, Soraia; Sousa, Flávia; Sarmento, Bruno

doi:10.1080/17425247.2019.1583205

Cited by 100 publications

(64 citation statements)

References 172 publications

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“…The blood-brain barrier (BBB) is a semipermeable membrane that carefully regulates the exchange of solutes between blood and brain to maintain CNS homeostasis and block entry of toxins and pathogens into the CNS (Bradbury, 1984;Abbott et al, 2010;Betsholtz, 2014;Daneman and Prat, 2015;Ferreira, 2019;Moura et al, 2019). The integrity of the BBB is largely dependent on its tight junctions (Brown and Davis, 2002;Castro Dias et al, 2019), adherens junction proteins, and ability to control the vesicular movement of macromolecules through transcytosis and pinocytosis (Dehouck et al, 1997;Baldo et al, 2014).…”

Section: Lipids and The Blood-brain Barriermentioning

confidence: 99%

Involvement of Lipids in Alzheimer’s Disease Pathology and Potential Therapies

2020

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Lipids constitute the bulk of the dry mass of the brain and have been associated with healthy function as well as the most common pathological conditions of the brain. Demographic factors, genetics, and lifestyles are the major factors that influence lipid metabolism and are also the key components of lipid disruption in Alzheimer's disease (AD). Additionally, the most common genetic risk factor of AD, APOE 4 genotype, is involved in lipid transport and metabolism. We propose that lipids are at the center of Alzheimer's disease pathology based on their involvement in the blood-brain barrier function, amyloid precursor protein (APP) processing, myelination, membrane remodeling, receptor signaling, inflammation, oxidation, and energy balance. Under healthy conditions, lipid homeostasis bestows a balanced cellular environment that enables the proper functioning of brain cells. However, under pathological conditions, dyshomeostasis of brain lipid composition can result in disturbed BBB, abnormal processing of APP, dysfunction in endocytosis/exocytosis/autophagocytosis, altered myelination, disturbed signaling, unbalanced energy metabolism, and enhanced inflammation. These lipid disturbances may contribute to abnormalities in brain function that are the hallmark of AD. The wide variance of lipid disturbances associated with brain function suggest that AD pathology may present as a complex interaction between several metabolic pathways that are augmented by risk factors such as age, genetics, and lifestyles. Herewith, we examine factors that influence brain lipid composition, review the association of lipids with all known facets of AD pathology, and offer pointers for potential therapies that target lipid pathways.

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Section: Lipids and The Blood-brain Barriermentioning

confidence: 99%

Involvement of Lipids in Alzheimer’s Disease Pathology and Potential Therapies

2020

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“…Hence, novel technologies and delivery systems are needed to overcome this barrier and release the drugs into the brain matrix. Nanotechnology-based drug delivery systems are a powerful method for drug transport into the brain [40,51,52]. A well-known candidate for CNS targeted delivery of drugs is colloidal-based particulate systems [53][54][55].…”

Section: Nano-scale Drug Delivery To the Brainmentioning

confidence: 99%

Multifunctional Polymeric Nanoplatforms for Brain Diseases Diagnosis, Therapy and Theranostics

et al. 2020

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The blood–brain barrier (BBB) acts as a barrier to prevent the central nervous system (CNS) from damage by substances that originate from the blood circulation. The BBB limits drug penetration into the brain and is one of the major clinical obstacles to the treatment of CNS diseases. Nanotechnology-based delivery systems have been tested for overcoming this barrier and releasing related drugs into the brain matrix. In this review, nanoparticles (NPs) from simple to developed delivery systems are discussed for the delivery of a drug to the brain. This review particularly focuses on polymeric nanomaterials that have been used for CNS treatment. Polymeric NPs such as polylactide (PLA), poly (D, L-lactide-co-glycolide) (PLGA), poly (ε-caprolactone) (PCL), poly (alkyl cyanoacrylate) (PACA), human serum albumin (HSA), gelatin, and chitosan are discussed in detail.

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“…In fact, 125 I-leptin uptake was considerately reduced in mice lacking LepR on endothelial cells compared to the normal mice in in situ brain perfusion assay. 41) Thus, LepR can be utilized for drug delivery into brain across the BBB; however, the expression level of LepR changed, depending on the conditions. Fatty diets induced LepR upregulation, which might influence the extent of drug uptake based on RMT through LepR.…”

Section: Insrmentioning

confidence: 99%

Smart Strategies for Therapeutic Agent Delivery into Brain across the Blood–Brain Barrier Using Receptor-Mediated Transcytosis

Tashima¹

2020

Chem. Pharm. Bull.

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Discriminatory drug delivery into target cells is essential to effectively elicit the drug activity and to avoid off-target side effects; however, transporting drugs across the cell membrane is difficult due to factors such as molecular size, hydrophilicity, intercellular adhesiveness, and efflux transporters, particularly, in the brain capillary endothelial cells. Drug delivery into the brain is blocked by the blood-brain barrier (BBB). Thus, developing drugs for the central nervous system (CNS) diseases remains a challenge. The approach based on receptor-mediated transcytosis (RMT) can overcome this impassable problem at the BBB. Well-designed molecules for RMT form conjugates with the ligand and drugs via linkers or nanoparticles. Cell penetrating peptides (CPPs), receptor-targeting peptides, and monoclonal antibodies (mAbs) are often used as ligands. The binding of ligand to the receptor on the endothelial cell surface induces endocytosis. Existing exosomes comprising the conjugates move in the cytoplasm and fuse with the opposite plasma membrane to release them. Subsequently, the transcytosed conjugate-loaded drugs or released drugs from the conjugates elicit activity in the brain. As receptors, transferrin receptor (TfR), low-density lipoprotein receptor (LDLR), and insulin receptor (InsR) have been used to intendedly induce transcytosis. Presently, several clinical trials on CNS drugs for Alzheimer's and Parkinson disease are hindered due to poor drug distribution into the brain. Therefore, this strategy based on RMT is a promising method for CNS drugs to be transported into the brain. In this review, I introduce the practicality and possibility of drug delivery into brain across the BBB using RMT.

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Blood-brain barrier receptors and transporters: an insight on their function and how to exploit them through nanotechnology

Cited by 100 publications

References 172 publications

Involvement of Lipids in Alzheimer’s Disease Pathology and Potential Therapies

Involvement of Lipids in Alzheimer’s Disease Pathology and Potential Therapies

Multifunctional Polymeric Nanoplatforms for Brain Diseases Diagnosis, Therapy and Theranostics

Smart Strategies for Therapeutic Agent Delivery into Brain across the Blood–Brain Barrier Using Receptor-Mediated Transcytosis

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