scholarly journals Gold Nanoparticles Crossing Blood-Brain Barrier Prevent HSV-1 Infection and Reduce Herpes Associated Amyloid-βsecretion

2020 ◽  
Vol 9 (1) ◽  
pp. 155 ◽  
Author(s):  
Rodriguez-Izquierdo I ◽  
Serramia MJ ◽  
Gomez R ◽  
De La Mata FJ ◽  
Bullido MJ ◽  
...  
Keyword(s):  
Gold Nanoparticles ◽  
Neurodegenerative Diseases ◽  
Cell Line ◽  
Blood Brain Barrier ◽  
Amyloid Β ◽  
Brain Barrier ◽  
Mice Model ◽  
Blood Brain ◽  
Hsv 1

Infections caused by HSV-1 and their typical outbreaks invading the nervous system have been related to neurodegenerative diseases. HSV-1 infection may deregulate the balance between the amyloidogenic and non-amyloidogenic pathways, raising the accumulation of amyloid-β peptides, one of the hallmarks in the neurodegenerative diseases. An effective treatment against both, HSV-1 infections and neurodegeneration, is a major therapeutic target. Therefore, gold nanoparticles (NPAus) have been previously studied in immunotherapy, cancer and cellular disruptions with very promising results. Our study demonstrates that a new NPAus family inhibits the HSV-1 infection in a neural-derived SK-N-MC cell line model and that this new NPAus reduces the HSV-1-induced β-secretase activity, as well as amyloid-β accumulation in SK-APP-D1 modifies cell line. We demonstrated that NPAuG3-S8 crosses the blood-brain barrier (BBB) and does not generate cerebral damage to in vivo CD1 mice model. The NPAuG3-S8 could be a promising treatment against neuronal HSV-1 infections and neuronal disorders related to the Aβ peptides.

scholarly journals Blood-brain barrier opening for facilitating drug delivery in neurological and neurodegenerative diseases in non-human primates

2018 ◽  
Author(s):  
Elisa E. Konofagou
Keyword(s):  
Neurodegenerative Diseases ◽  
Blood Brain Barrier ◽  
Focused Ultrasound ◽  
Neurological Diseases ◽  
Brain Barrier ◽  
Blood Brain ◽  
Therapeutic Molecules ◽  
After Cancer ◽  
Large Animals

After cancer and heart disease, neurodegenerative diseases, such as Alzheimer's, Parkinson's, multiple sclerosis (MS), amythrophic lateral sclerosis (ALS), and neurological diseases take more lives each year than any other illness. Although great progress has been made in recent years toward understanding of central nervous system (CNS) diseases, few effective treatments and no cures are currently available. This is mainly because the blood-brain barrier (BBB) limits the delivery of the vast majority of systemically-administered drugs available to treat those diseases. The underlying hypothesis of this study is that delivery of therapeutic molecules is safe and effective through the blood-brain barrier (BBB) using Focused Ultrasound (FUS) in large animals in vivo. Our preliminary results have shown that the FUS technique can induce BBB opening entirely noninvasively, selectively and be monitored with MRI at sub-millimeter resolution in vivo. The specific aims are therefore to: 1) build a MRcompatible system for FUS targeting and monitoring in the MRI system; 2) test and demonstrate delivery of neurotrophic factors to the hippocampus and putamen of monkeys; 3) test and demonstrate delivery of inhibitors to the visual cortex of monkeys; and 4) assess the safety of the FUS method in monkeys.

scholarly journals Blood-Brain Barrier Permeable 2-Phenylbenzothiazolyl Iridi-um Complexes as Inhibitors and Probes of Aβ Aggregation

2021 ◽  
Author(s):  
Yiran Huang ◽  
Hanah Na ◽  
Liang Sun ◽  
Karna Terpstra ◽  
Kai Gui ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Day Treatment ◽  
Amyloid Β ◽  
Brain Barrier ◽  
Blood Brain ◽  
Aβ Aggregation ◽  
D Values ◽  
Aβ Fibrils

The aggregation of amyloid β (Aβ) peptides is a significant hallmark of Alzheimer’s Disease (AD) and the inhibition and detection of Aβ aggregates are important for the treatment and diagnosis of AD. Herein, a series of benzothiazole-based luminescent Ir(III) complexes <b>HN-1</b> to <b>HN-8</b> were reported, which exhibit appreciable Aβ aggregation inhibition ability <i>in vitro</i> and in living cells. In addition, they are capable of inducing a fluorescence turn-on effect when binding to Aβ fibrils and oligomers. Most importantly, compared to previously reported cationic metal complexes, the neutral Ir complexes reported here show optimal Log D values, which suggest these compounds should have enhanced blood brain barrier (BBB) permeability. Most importantly, <i>in vivo</i> studies show that the neutral Ir complexes <b>HN-2</b>, <b>HN-3</b>, and <b>HN-8</b> successfully penetrate the BBB and stain amyloid plaques in AD mice brains after a 10-day treatment via i.p. injection, which is unprecedented for Ir(III) complexes, and thus can be used as lead compounds for AD therapeutics development.

scholarly journals Blood-Brain Barrier Permeable 2-Phenylbenzothiazolyl Iridi-um Complexes as Inhibitors and Probes of Aβ Aggregation

2021 ◽  
Author(s):  
Yiran Huang ◽  
Hanah Na ◽  
Liang Sun ◽  
Karna Terpstra ◽  
Kai Gui ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Day Treatment ◽  
Amyloid Β ◽  
Brain Barrier ◽  
Blood Brain ◽  
Aβ Aggregation ◽  
D Values ◽  
Aβ Fibrils

The aggregation of amyloid β (Aβ) peptides is a significant hallmark of Alzheimer’s Disease (AD) and the inhibition and detection of Aβ aggregates are important for the treatment and diagnosis of AD. Herein, a series of benzothiazole-based luminescent Ir(III) complexes <b>HN-1</b> to <b>HN-8</b> were reported, which exhibit appreciable Aβ aggregation inhibition ability <i>in vitro</i> and in living cells. In addition, they are capable of inducing a fluorescence turn-on effect when binding to Aβ fibrils and oligomers. Most importantly, compared to previously reported cationic metal complexes, the neutral Ir complexes reported here show optimal Log D values, which suggest these compounds should have enhanced blood brain barrier (BBB) permeability. Most importantly, <i>in vivo</i> studies show that the neutral Ir complexes <b>HN-2</b>, <b>HN-3</b>, and <b>HN-8</b> successfully penetrate the BBB and stain amyloid plaques in AD mice brains after a 10-day treatment via i.p. injection, which is unprecedented for Ir(III) complexes, and thus can be used as lead compounds for AD therapeutics development.

Engineered models for studying blood-brain-barrier-associated brain physiology and pathology

Organoid ◽  
2021 ◽  
Vol 1 ◽  
pp. e10
Author(s):  
Hong Nam Kim
Keyword(s):  
Neurodegenerative Diseases ◽  
Blood Brain Barrier ◽  
Three Dimensional ◽  
Brain Barrier ◽  
Sufficient Information ◽  
Transport Barrier ◽  
Brain Physiology ◽  
Blood Brain ◽  
The Brain

The blood-brain barrier (BBB) is a transport barrier that suppresses the translocation of potentially harmful substances to the brain tissue. Although the BBB is known to be associated with many kinds of neuropathology, such as neuroinflammation and neurodegenerative diseases, the conventionally used animal and Transwell models cannot provide sufficient information due to genetic and functional heterogeneity in comparison with humans and limited monitoring capabilities. Recently, human cell-based three-dimensional BBB models have been developed, and these models provide in vivo-like BBB structures and functions. In this review, we provide an overview of the recent advances in BBB models with a particular focus on the simulation of BBB-associated brain physiology and neuropathology. To this end, important factors for recapitulating the in vivo characteristics of the BBB are described. Furthermore, approaches to recapitulate the BBB physiology using engineering methods are summarized. The applications of BBB models in the study of neuropathology, such as inflammation and neurodegenerative diseases, are also presented.

An immortalised astrocyte cell line maintains the in vivo phenotype of a primary porcine in vitro blood–brain barrier model

2012 ◽  
Vol 1479 ◽  
pp. 17-30 ◽  
Author(s):  
Carina A. Cantrill ◽  
Robert A. Skinner ◽  
Nancy J. Rothwell ◽  
Jeffrey I. Penny
Keyword(s):  
Cell Line ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Blood Brain ◽  
Blood Brain Barrier Model ◽  
Barrier Model

Amyloid-β Aggregation Inhibitory and Neuroprotective Effects of Xanthohumol and its Derivatives for Alzheimer’s Diseases

2019 ◽  
Vol 16 (9) ◽  
pp. 836-842 ◽  
Author(s):  
Xueli Wang ◽  
See-Lok Ho ◽  
Chung-Yan Poon ◽  
Ting Yan ◽  
Hung-Wing Li ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Amyloid Β ◽  
Inhibitory Effect ◽  
Brain Barrier ◽  
Ros Generation ◽  
Neuroprotective Effects ◽  
Drug Candidates ◽  
Blood Brain ◽  
Brain Barrier Permeability

Background: Xanthohumol has been reported to have cytoprotection through activation of Nrf2−ARE signaling pathway and; it has capability of scavenging free radicals, suggesting its potential for the prevention of neurodegeneration. However, the bio-incompatibility and blood-brain barrier impermeability of xanthohumol hindered its in vivo efficacy potential for treating Alzheimer’s disease (AD). Objective: We designed and prepared a series of xanthohumol derivatives to enhance the desirable physical, biological and pharmacological properties in particular the blood-brain barrier permeability for intervention of AD. Methods: We designed and synthesized a novel series of 9 xanthohumol derivatives. Their inhibitory effect on amyloid-β (1-42), Aβ1-42, oligomerization and fibrillation as well as neuroprotection against amyloid-β induced toxicities, were explored. Results: Among the 9 xanthohumol derivatives, some of them exhibited a moderate to high inhibitory effect on Aβ1-42 oligomerization and fibrillation. They were biocompatible and neuroprotective to the SH-SY5Y cells by reducing the ROS generation and calcium uploading that were induced by the amyloid- β. Importantly, two of the derivatives were found to be blood-brain barrier permeable showing promising potential for AD treatment. Conclusion: Two derivatives have been identified to be biocompatible, non-toxic, neuroprotective against Aβ-induced toxicities and blood-brain barrier permeable highlighting their promising potential as AD drug candidates for future clinical use.

P2-325: In VIVO labeling of amyloid β plaques in AD model mice using blood-brain barrier permeable styryl dyes

2006 ◽  
Vol 2 ◽  
pp. S336-S336
Author(s):  
Hueizhi Wu ◽  
Yong Ji ◽  
Henrieta Scholtzova ◽  
Qian Li ◽  
Martin Sadowski ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Amyloid Β ◽  
Brain Barrier ◽  
Styryl Dyes ◽  
Blood Brain ◽  
In Vivo Labeling

scholarly journals β-Amyloid Protein Induces Mitophagy-Dependent Ferroptosis Through the CD36/PINK/PARKIN Pathway Leading to Blood-Brain Barrier Destruction in Alzheimer's Disease

2021 ◽  
Author(s):  
li Jianhua ◽  
Li mengyu ◽  
Ge Yangyang ◽  
Chen Jiayi ◽  
Ma Jiamin ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Molecular Mechanism ◽  
Blood Brain Barrier ◽  
Amyloid Β ◽  
Brain Barrier ◽  
Blood Brain ◽  
Bbb Permeability

Abstract Background Blood-brain barrier (BBB) dysfunction may occur in the onset of Alzheimer's disease (AD). While pericytes are a vital part of the neurovascular unit and the BBB, acting as the gatekeeper of the BBB. Amyloid β (Aβ) deposition and neurofibrillary tangles in the brain are the central pathological features of AD. CD36 promotes vascular amyloid deposition and leads to vascular brain damage, neurovascular dysfunction, and cognitive deficits. However, the molecular mechanism in destroying pericytes of the BBB are still unclear. Objectives To investigate the effect of low-dose Aβ1-40 administration on pericyte outcome and BBB injury molecular mechanism. Methods We selected 6-month-old and 9-month-old APP/PS1 mice and wild-type (WT) mice of the same strain, age, and sex as controls. We assessed the BBB by PET/CT. Brain pericytes were extracted and cocultured with endothelial cells (bEnd.3) to generate an in vitro BBB model to observe the effect of Aβ1-40 on the BBB. Furthermore, we explored the intracellular degradation and related molecular mechanisms of Aβ1-40 after being engulfed in cells through CD36. Results BBB permeability and the number of pericytes decreased in APP/PS1 mice. Aβ1-40 increases the permeability of the BBB in an in vivo model and downregulates the expression of CD36, which reversed the Aβ-induced changes in BBB permeability. Aβ1-40 was phagocytized in pericytes with high expression of CD36. We observed that this molecule inhibited pericyte proliferation, caused mitochondrial damage, and increased mitophagy. Finally, we confirmed that Aβ1-40 induced pericyte mitophagy-dependent ferroptosis through the CD36/PINK1/Parkin pathway. Conclusions PDGFRβ (a marker of pericytes), CD36, and amyloid β colocalized in vitro and in vivo and that Aβ1-40 caused BBB destruction by upregulating the expression of CD36 in pericytes. The mechanism by which Aβ1-40 destroys the BBB involves induction of pericyte mitophagy-dependent ferroptosis through the CD36/PINK1/Parkin pathway.

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