Transferrin' bispecific antibodies across the blood–brain barrier

Bray, Natasha

doi:10.1038/nrd4522

Cited by 15 publications

(10 citation statements)

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“…2). For example, the large neutral amino acid CMT transporter delivers L-3,4-dihydroxyphenylalanine (L-DOPA) to the brain in PD 240 , and the transferrin RMT can deliver therapeutic antibodies to the brain in various neurological conditions 4,241–243 . Other approaches, such as using nanoparticles 244 and/or opening the BBB by focused ultrasound 245,246 to improve the delivery of therapeutic agents to CNS, have been attempted.…”

Section: How Bbb Breakdown Affects Drug Deliverymentioning

confidence: 99%

Blood–brain barrier breakdown in Alzheimer disease and other neurodegenerative disorders

2018

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The blood–brain barrier (BBB) is a continuous endothelial membrane within brain microvessels that has sealed cell-to-cell contacts, and is sheathed by mural vascular cells and perivascular astrocyte end-feet. The BBB protects neurons from factors present in the systemic circulation, and maintains the highly regulated CNS internal milieu, which is required for proper synaptic and neuronal functioning. BBB disruption allows influx into the brain of neurotoxic blood-derived debris, cells, and microbial pathogens, and is associated with inflammatory and immune responses, which can initiate multiple pathways of neurodegeneration. This Review discusses neuroimaging studies in the living human brain, post-mortem tissue and biomarker studies demonstrating BBB breakdown in Alzheimer disease, Parkinson disease, Huntington disease, amyotrophic lateral sclerosis, multiple sclerosis, HIV-1-associated dementia and chronic traumatic encephalopathy. The pathogenic mechanisms by which BBB breakdown leads to neuronal injury, synaptic dysfunction, loss of neuronal connectivity and neurodegeneration are described. The importance of a healthy BBB for therapeutic drug delivery, and the adverse effects of disease-initiated, pathological BBB breakdown in relation to brain delivery of neuropharmaceuticals are briefly discussed. Finally, future directions, gaps in the field and opportunities to control the course of neurological diseases by targeting BBB are presented.

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Section: How Bbb Breakdown Affects Drug Deliverymentioning

confidence: 99%

Blood–brain barrier breakdown in Alzheimer disease and other neurodegenerative disorders

2018

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“…For example, Aβ can cross the BBB to enter the circulation through LRP1 (Deane et al, 2004) or the other way around via the receptor for advanced glycation end products (RAGE) on RAGE-expressing endothelium, particularly under pathological conditions (Deane et al, 2003, 2012). Moreover, RMT systems, for example the transferrin receptor (TfR), have been utilized for the CNS drug delivery (Bray, 2015). …”

Section: Cellular Components Of the Bbbmentioning

confidence: 99%

Establishment and Dysfunction of the Blood-Brain Barrier

Zhao

Nelson

Betsholtz³

et al. 2015

Cell

1,263

1,128

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Structural and functional brain connectivity, synaptic activity and information processing require highly coordinated signal transduction between different cell types within the neurovascular unit and intact blood-brain barrier (BBB) functions. Here, we examine the mechanisms regulating the formation and maintenance of the BBB and functions of BBB-associated cell types. Furthermore, we discuss the growing evidence associating BBB breakdown with the pathogenesis of inherited monogenic neurological disorders and complex multifactorial diseases including Alzheimer’s disease.

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“…A promising solution to solve this problem is the focused ultrasound therapy, which employs controlled high‐frequency ultrasound pulses to shortly disrupt the BBB and allow passage of bigger molecules into the brain . Other approaches make use of native BBB transporters such as transferrin‐1, which can actively pass molecules from the plasma into the brain .…”

Section: Different Treatment Approaches Based On Pathogenesismentioning

confidence: 99%

“…Other approaches make use of native BBB transporters such as transferrin-1, which can actively pass molecules from the plasma into the brain [354,355].…”

Section: Passive Immunotherapiesmentioning

confidence: 99%

Current and emerging avenues for Alzheimer's disease drug targets

et al. 2019

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Loera-Valencia R, Cedazo-Minguez A, ). Current and emerging avenues for Alzheimer's disease drug targets (Review). J Intern Med 2019; 286: 398-437.Alzheimer's disease (AD), the most frequent cause of dementia, is escalating as a global epidemic, and so far, there is neither cure nor treatment to alter its progression. The most important feature of the disease is neuronal death and loss of cognitive functions, caused probably from several pathological processes in the brain. The main neuropathological features of AD are widely described as amyloid beta (Ab) plaques and neurofibrillary tangles of the aggregated protein tau, which contribute to the disease. Nevertheless, AD brains suffer from a variety of alterations in function, such as energy metabolism, inflammation and synaptic activity. The latest decades have seen an explosion of genes and molecules that can be employed as targets aiming to improve brain physiology, which can result in preventive strategies for AD. Moreover, therapeutics using these targets can help AD brains to sustain function during the development of AD pathology. Here, we review broadly recent information for potential targets that can modify AD through diverse pharmacological and nonpharmacological approaches including gene therapy. We propose that AD could be tackled not only using combination therapies including Ab and tau, but also considering insulin and cholesterol metabolism, vascular function, synaptic plasticity, epigenetics, neurovascular junction and blood-brain barrier targets that have been studied recently. We also make a case for the role of gut microbiota in AD. Our hope is to promote the continuing research of diverse targets affecting AD and promote diverse targeting as a near-future strategy. ReviewInsoluble Ab fibrils are taken into consideration as the main responsible for spine pathology. On the other hand, in both transgenic mouse models of AD and human AD brain, synapse defects and memory loss correlate weakly with the presence of Ab Current and novel Alzheimer´s disease therapy targets / R. Loera-Valencia et al.

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Transferrin' bispecific antibodies across the blood–brain barrier

Cited by 15 publications

References 1 publication

Blood–brain barrier breakdown in Alzheimer disease and other neurodegenerative disorders

Blood–brain barrier breakdown in Alzheimer disease and other neurodegenerative disorders

Establishment and Dysfunction of the Blood-Brain Barrier

Current and emerging avenues for Alzheimer's disease drug targets

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