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

Nature Reviews Neurology, Год журнала: 2018, Номер 14(3), С. 133 - 150

Опубликована: Янв. 29, 2018

Язык: Английский

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Blood-Brain Barrier: From Physiology to Disease and Back

Physiological Reviews, Год журнала: 2018, Номер 99(1), С. 21 - 78

Опубликована: Окт. 3, 2018

The blood-brain barrier (BBB) prevents neurotoxic plasma components, blood cells, and pathogens from entering the brain. At same time, BBB regulates transport of molecules into out central nervous system (CNS), which maintains tightly controlled chemical composition neuronal milieu that is required for proper functioning. In this review, we first examine molecular cellular mechanisms underlying establishment BBB. Then, focus on physiology, endothelial pericyte transporters, perivascular paravascular transport. Next, discuss rare human monogenic neurological disorders with primary genetic defect in BBB-associated cells demonstrating link between breakdown neurodegeneration. review effects genes inheritance and/or increased susceptibility Alzheimer's disease (AD), Parkinson's (PD), Huntington's disease, amyotrophic lateral sclerosis (ALS) relation to other pathologies deficits. We next how dysfunction relates deficits majority sporadic AD, PD, ALS cases, multiple sclerosis, neurodegenerative disorders, acute CNS such as stroke, traumatic brain injury, spinal cord epilepsy. Lastly, BBB-based therapeutic opportunities. conclude lessons learned future directions, emphasis technological advances investigate functions living brain, at level, address key unanswered questions.

Язык: Английский

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Molecular Diversity and Specializations among the Cells of the Adult Mouse Brain

Cell, Год журнала: 2018, Номер 174(4), С. 1015 - 1030.e16

Опубликована: Авг. 1, 2018

Язык: Английский

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Cerebral blood flow regulation and neurovascular dysfunction in Alzheimer disease

Nature reviews. Neuroscience, Год журнала: 2017, Номер 18(7), С. 419 - 434

Опубликована: Май 18, 2017

Язык: Английский

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The hypoxic tumour microenvironment

Oncogenesis, Год журнала: 2018, Номер 7(1)

Опубликована: Янв. 22, 2018

Cancer progression often benefits from the selective conditions present in tumour microenvironment, such as presence of cancer-associated fibroblasts (CAFs), deregulated ECM deposition, expanded vascularisation and repression immune response. Generation a hypoxic environment activation its main effector, hypoxia-inducible factor-1 (HIF-1), are common features advanced cancers. In addition to impact on cell biology, influence that hypoxia exerts surrounding cells represents critical step tumorigenic process. Hypoxia indeed enables number events microenvironment lead expansion aggressive clones heterogeneous promote lethal phenotype. this article, we review most relevant findings describing contribution HIF major components summarise their role cancer development progression.

Язык: Английский

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The role of brain vasculature in neurodegenerative disorders

Nature Neuroscience, Год журнала: 2018, Номер 21(10), С. 1318 - 1331

Опубликована: Сен. 19, 2018

Язык: Английский

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Functional morphology of the blood–brain barrier in health and disease

Acta Neuropathologica, Год журнала: 2018, Номер 135(3), С. 311 - 336

Опубликована: Фев. 6, 2018

The adult quiescent blood–brain barrier (BBB), a structure organised by endothelial cells through interactions with pericytes, astrocytes, neurons and microglia in the neurovascular unit, is highly regulated but fragile at same time. In past decade, there has been considerable progress understanding not only molecular pathways involved BBB development, also breakdown neurological diseases. Specifically, Wnt/β-catenin, retinoic acid sonic hedgehog moved into focus of research. Moreover, angiopoietin/Tie2 signalling that linked to angiogenic processes gained attention field. Blood vessels play an essential role initiation progression many diseases, including inflammation outside central nervous system (CNS). Therefore, potential influence CNS blood diseases associated alterations or neuroinflammation become major current research understand their contribution pathogenesis. remains obstacle pharmaceutical intervention CNS. complications may either be expressed inadequate therapeutic delivery like brain tumours, poor drug across ineffective bioavailability. this review, we initially describe cellular components contribute steady state healthy BBB. We then discuss ischaemic stroke, primary metastatic tumour, chronic Alzheimer's disease. Throughout highlight common mechanisms abnormalities among these particular dysfunction disease progression, emphasise unique aspects alteration certain such as tumours. review highlights novel strategies monitor function non-invasive imaging techniques focussing on well ways modulate permeability promote treatment conclusion, deep signals maintain fluctuations states will key elucidate identify targets for diagnostics modulation

Язык: Английский

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3D self-organized microvascular model of the human blood-brain barrier with endothelial cells, pericytes and astrocytes

Biomaterials, Год журнала: 2018, Номер 180, С. 117 - 129

Опубликована: Июль 13, 2018

The blood-brain barrier (BBB) regulates molecular trafficking, protects against pathogens, and prevents efficient drug delivery to the brain. Models date failed reproduce human anatomical complexity of brain barriers, contributing misleading results in clinical trials. To overcome these limitations, a novel 3-dimensional BBB microvascular network model was developed via vasculogenesis accurately replicate vivo neurovascular organization. This microfluidic system includes induced pluripotent stem cell-derived endothelial cells, pericytes, astrocytes as self-assembled vascular networks fibrin gel. Gene expression membrane transporters, tight junction extracellular matrix proteins, consistent with computational analysis geometrical structures quantitative immunocytochemistry, indicating maturation microenvironment remodelling. Confocal microscopy validated microvessel-pericyte/astrocyte dynamic contact-interactions. exhibited perfusable selective microvasculature, permeability lower than conventional vitro models, similar measurements rat robust physiologically relevant offers an innovative valuable platform for discovery predict neuro-therapeutic transport efficacy pre-clinical applications well recapitulate patient-specific pathological functions neurodegenerative disease.

Язык: Английский

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Alzheimer’s disease: A matter of blood–brain barrier dysfunction?

The Journal of Experimental Medicine, Год журнала: 2017, Номер 214(11), С. 3151 - 3169

Опубликована: Окт. 23, 2017

The blood-brain barrier (BBB) keeps neurotoxic plasma-derived components, cells, and pathogens out of the brain. An early BBB breakdown and/or dysfunction have been shown in Alzheimer's disease (AD) before dementia, neurodegeneration brain atrophy occur. However, role neurodegenerative disorders is still not fully understood. Here, we examine animal models frequently used to study pathophysiology AD, including transgenic mice expressing human amyloid-β precursor protein, presenilin 1, tau mutations, apolipoprotein E, strongest genetic risk factor for AD. We discuss process, pitfalls measurements, how targeting can influence course neurological disorder. Finally, comment on future approaches better define, at cellular molecular level, underlying mechanisms between as a basis developing new therapies repair control neurodegeneration.

Язык: Английский

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The Lymphatic Vasculature in the 21st Century: Novel Functional Roles in Homeostasis and Disease

Cell, Год журнала: 2020, Номер 182(2), С. 270 - 296

Опубликована: Июль 1, 2020

Язык: Английский

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