
Annette BurkhartAalborg University · Department of Health Science and Technology
Annette Burkhart
PhD
About
38
Publications
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Introduction
Additional affiliations
June 2021 - present
September 2011 - September 2014
June 2017 - May 2021
Education
September 2009 - June 2011
September 2007 - June 2009
September 2004 - June 2007
Publications
Publications (38)
Background
Patients with the genetic disorder Niemann-Pick type C2 disease (NP-C2) suffer from lysosomal accumulation of cholesterol causing both systemic and severe neurological symptoms. In a murine NP-C2 model, otherwise successful intravenous Niemann-Pick C2 protein (NPC2) replacement therapy fails to alleviate progressive neurodegeneration as...
Introduction:
Niemann-Pick type C2 disease (NP-C2) is a fatal neurovisceral disorder caused by defects in the lysosomal cholesterol transporter protein NPC2. Consequently, cholesterol and other lipids accumulate within the lysosomes, causing a heterogeneous spectrum of clinical manifestations. Murine models are essential for increasing the underst...
Treating central nervous system (CNS) diseases is complicated by the incapability of numerous therapeutics to cross the blood–brain barrier (BBB), mainly composed of brain endothelial cells (BECs). Genetically modifying BECs into protein factories that supply the CNS with recombinant proteins is a promising approach to overcome this hindrance, espe...
Treatment of many diseases affecting the central nervous system (CNS) is complicated by the inability of several therapeutics to cross the blood–brain barrier (BBB). Genetically modifying brain capillary endothelial cells (BCECs) denotes an approach to overcome the limitations of the BBB by turning BCECs into recombinant protein factories. This wil...
Treatment of chronic disorders affecting the central nervous system (CNS) is complicated by the inability of drugs to cross the blood–brain barrier (BBB). Non-viral gene therapy applied to brain capillary endothelial cells (BCECs) denotes a novel approach to overcome the restraints in this passage, as turning BCECs into recombinant protein factorie...
Background and objectives: Brain capillary endothelial cells (BCECs) express transferrin receptor 1 (TfR1) to ensure sufficient iron transport into the brain across the blood-brain barrier (BBB). Our main objective was to examine adult mice subjected to dietary iron deficiency (ID) for possible changes in the content of TfR1 in BCECs and the influe...
Neurodegenerative diseases are often accompanied by neuroinflammation and impairment of the blood-brain barrier (BBB) mediated by activated glial cells through their release of proinflammatory molecules. To study the effects of glial cells on mouse brain endothelial cells (mBECs), we developed an in vitro BBB model with inflammation by preactivatin...
Background: Patients with the genetic disorder Niemann-Pick type C2 disease (NP-C2) suffer from lysosomal accumulation of cholesterol causing both systemic and severe neurological symptoms. In a murine NP-C2 model, otherwise successful intravenous Niemann-Pick C2 protein (NPC2) replacement therapy fails to alleviate progressive neurodegeneration as...
Background/Objectives: Iron (Fe) is a co-factor for enzymes of the developing brain necessitating sufficient supply. We investigated the effects of administering ferric derisomaltose/Fe isomaltoside (FDI) subcutaneously to Fe-deficient (ID) pregnant rats on cerebral and hepatic concentrations of essential metals and the expression of iron-relevant...
The blood-brain barrier (BBB) formed by brain endothelial cells (BECs) limits the passage of biopharmaceuticals from the circulation into the brain parenchyma. An emerging strategy suggests that viral vectors may specifically target and productively transduce BECs leading to protein secretion into the brain. To study protein secretion, different AA...
Purpose
The blood-brain barrier (BBB), formed by brain endothelial cells (BECs) ensures a stable microenvironment inside the brain by regulating transport of blood-borne molecules to the brain. However, neurodegenerative diseases are often accompanied by neuroinflammation and BBB impairment mediated by activated glial cells through their release of...
Iron (Fe) is co-factor for enzymes of the developing brain necessitating sufficient supply. We investigated the effects of administering ferric derisomaltose/Fe isomaltoside (FDI) subcutaneously to Fe deficient (ID) pregnant rats on cerebral and hepatic concentrations of essential metals and gene expression of ferroportin and hepcidin. Pregnant rat...
Background: Patients with the genetic disorder Niemann-Pick type C2 disease (NP-C2) suffer from lysosomal accumulation of cholesterol causing both systemic and severe neurological symptoms. In a murine NP-C2 model, otherwise successful intravenous Niemann-Pick C2 protein (NPC2) replacement therapy fails to alleviate progressive neurodegeneration as...
Background
Patients with the genetic disorder Niemann-Pick type C2 disease (NP-C2) suffer from lysosomal accumulation of cholesterol causing both systemic and severe neurological symptoms. In a murine NP-C2 model, otherwise successful intravenous Niemann-Pick C2 protein (NPC2) replacement therapy fails to alleviate progressive neurodegeneration as...
Introduction:
The treatment of neurological diseases is significantly hampered by the lack of available therapeutics. A major restraint for the development of drugs is denoted by the presence of the blood-brain barrier (BBB), which precludes the transfer of biotherapeutics to the brain due to size restraints.
Areas covered:
Novel optimism for tr...
Inhibition of the interaction between the scaffolding protein PSD-95 and the NMDA receptor has been shown to obstruct ischemic stroke-triggered excitotoxic reactions, leading to neuronal death. The peptides NR2B9c and N-dimer are inhibitors of this interaction. Delivery of the peptides to the brain is challenging due to the general low blood–brain...
Brain homeostasis depends on the existence of the blood–brain barrier (BBB). Despite decades of research, the factors and signalling pathways for modulating and maintaining BBB integrity are not fully elucidated. Here, we characterise the expression and function of the multifunctional receptor, sortilin, in the cells of the BBB, in vivo and in vitr...
The blood-brain barrier (BBB) is formed by brain capillary endothelial cells (BECs) supported by pericytes and astrocytes. The BBB maintains homeostasis and protects the brain against toxic substances circulating in the blood, meaning that only a few drugs can pass the BBB. Thus, for drug screening, understanding cell interactions, and pathology, i...
Ferroportin plays an essential role for iron transport through the blood-brain barrier (BBB), which is formed by brain capillary endothelial cells (BCECs). To maintain the integrity of the BBB, the BCECs gain support from pericytes and astrocytes, which together with neurons form the neurovascular unit (NVU). The objectives of the present study wer...
The blood-brain barrier (BBB) is formed by brain capillary endothelial cells (BECs) supported by pericytes and astrocytes. The BBB maintains homeostasis and protects the brain against toxic substances circulating in the blood, which consequently means that only a few drugs can pass the BBB. Thus for drug screening, understanding cell interactions,...
Obtaining efficient drug delivery to the brain remains the biggest challenge for the development of therapeutics to treat diseases of the central nervous system. The main obstacle is the blood-brain barrier (BBB), which impedes the entrance of most molecules present in the systemic circulation, especially large molecule drugs and nanomedicines. To...
Ferroportin is the only known iron exporter, and its regulation seems to be controlled at both transcriptional, post-transcriptional, and post-translational levels. The objective of the current work was to investigate how cellular iron status affects the expression of the ferroportin gene Fpn under the influence of hepcidin, known to post-translati...
The original version of this article unfortunately contained mistakes on Figs. 1, 2, and 7 as some of the data were not visible. With this, the correct images are hereby published.
Transport of the majority of therapeutic molecules to the brain is precluded by the presence of the blood-brain barrier (BBB) rendering efficient treatment of many neurological disorders impossible. This BBB, nonetheless, may be circumvented by targeting receptors and transport proteins expressed on the luminal surface of the brain capillary endoth...
Rationale: The ability to treat invalidating neurological diseases is impeded by the presence of the blood-brain barrier (BBB), which inhibits the transport of most blood-borne substances into the brain parenchyma. Targeting the transferrin receptor (TfR) on the surface of brain capillaries has been a popular strategy to give a preferential accumul...
Drug delivery to the brain is hampered by the presence of the blood-brain barrier, which excludes most molecules from freely diffusing into the brain, and tightly regulates the active transport mechanisms that ensure sufficient delivery of nutrients to the brain parenchyma. Harnessing the possibility of delivering neuroactive drugs by way of recept...
The mechanisms for iron transport through the blood-brain barrier (BBB) remain a controversy. We analyzed for expression of mRNA and proteins involved in oxidation and transport of iron in isolated brain capillaries from dietary normal, iron-deficient, and iron-reverted rats. The expression was also investigated in isolated rat brain endothelial ce...
The brain vascular basement membrane is important for both blood–brain barrier (BBB) development, stability, and barrier integrity and the contribution hereto from brain capillary endothelial cells (BCECs), pericytes, and astrocytes of the BBB is probably significant. The aim of this study was to analyse four different in vitro models of the murine...
Primary brain capillary endothelial cells (BCECs) are a promising tool to study the blood-brain barrier (BBB) in vitro, as they maintain many important characteristics of the BBB in vivo, especially when co-cultured with pericytes and/or astrocytes. A novel strategy for drug delivery to the brain is to transform BCECs into protein factories by gene...
In vitro blood-brain barrier (BBB) models based on primary brain endothelial cells (BECs) cultured as monoculture or in co-culture with primary astrocytes and pericytes are useful for studying many properties of the BBB. The BECs retain their expression of tight junction proteins and efflux transporters leading to high trans-endothelial electric re...
Iron is required in a variety of essential processes in the body. In this review, we focus on iron transport in the brain and the role of the divalent metal transporter 1 (DMT1) vital for iron uptake in most cells. DMT1 locates to cellular membranes and endosomal membranes, where it is a key player in non-transferrin bound iron uptake and transferr...
The brain is protected from the entry of unwanted substances by means of the blood-brain barrier (BBB) formed by the brain microvasculature. This BBB is composed of non-fenestrated brain capillary endothelial cells (BCECs) with their intermingling tight junctions. The presence of the BBB is a huge obstacle for the treatment of central nervous syste...
The blood-brain barrier (BBB), formed by brain capillary endothelial cells, prevents the entry of several drug molecules to the brain, especially molecules hydrophilic in nature. Advanced drug carriers like nanoparticles share the potential to allow entry of therapeutic proteins and genetic molecules into the central nervous system (CNS). Taking a...
Brain capillary endothelial cells form the blood-brain barrier (BBB) that denotes a major restraint for drug entry to the brain. The identification of many new targets to treat diseases in the brain demands novel thinking in drug design as new therapeutics could often be proteins and molecules of genetic origins like siRNA, miRNA and cDNA. Such mol...