Role of Angiopoietin-2 in Vascular Physiology and Pathophysiology

Cells, Год журнала: 2019, Номер 8(5), С. 471 - 471

Опубликована: Май 17, 2019

Angiopoietins 1–4 (Ang1–4) represent an important family of growth factors, whose activities are mediated through the tyrosine kinase receptors, Tie1 and Tie2. The best characterized angiopoietin-1 (Ang1) angiopoietin-2 (Ang2). Ang1 is a potent angiogenic factor signaling Tie2, whereas Ang2 was initially identified as vascular disruptive agent with antagonistic activity same receptor. Recent data demonstrates that has context-dependent agonist activities. plays roles in physiological processes deregulation its expression characteristic several diseases. In this review, we summarize on blood lymphatic endothelial cells, significance human physiology disease, provide current view molecular pathways regulated by cells.

Язык: Английский

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The blood-brain barrier in aging and neurodegeneration

Molecular Psychiatry, Год журнала: 2022, Номер 27(6), С. 2659 - 2673

Опубликована: Март 31, 2022

Abstract The blood-brain barrier (BBB) is vital for maintaining brain homeostasis by enabling an exquisite control of exchange compounds between the blood and parenchyma. Moreover, BBB prevents unwanted toxins pathogens from entering brain. This barrier, however, breaks down with age further disruption a hallmark many age-related disorders. Several drugs have been explored, thus far, to protect or restore function. With recent connection gut microbiota, microbial-derived metabolites explored their capabilities physiology. review, will focus on components that make up BBB, dissect levels discuss current therapeutics maintain integrity discoveries effects

Язык: Английский

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Endothelial activation and dysfunction in COVID-19: from basic mechanisms to potential therapeutic approaches

Signal Transduction and Targeted Therapy, Год журнала: 2020, Номер 5(1)

Опубликована: Дек. 24, 2020

Abstract On 12 March 2020, the outbreak of coronavirus disease 2019 (COVID-19) was declared a pandemic by World Health Organization. As 4 August more than 18 million confirmed infections had been reported globally. Most patients have mild symptoms, but some develop respiratory failure which is leading cause death among COVID-19 patients. Endothelial cells with high levels angiotensin-converting enzyme 2 expression are major participants and regulators inflammatory reactions coagulation. Accumulating evidence suggests that endothelial activation dysfunction participate in pathogenesis altering integrity vessel barrier, promoting pro-coagulative state, inducing inflammation, even mediating leukocyte infiltration. This review describes proposed cellular molecular mechanisms during emphasizing principal mediators therapeutic implications.

Язык: Английский

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Brain Microvascular Pericytes in Vascular Cognitive Impairment and Dementia

Frontiers in Aging Neuroscience, Год журнала: 2020, Номер 12

Опубликована: Апрель 14, 2020

Pericytes are unique, multi-functional mural cells localized at the abluminal side of perivascular space in microvessels. Originally discovered nineteenth century, pericytes had drawn less attention until decades ago mainly due to lack specific markers. Recently, however, a growing body evidence has revealed that play various important roles: development and maintenance blood-brain barrier (BBB), regulation neurovascular system (e.g., vascular stability, vessel formation, cerebral blood flow, etc.), trafficking inflammatory cells, clearance toxic waste products from brain, acquisition stem cell-like properties. In unit, perform these functions through coordinated crosstalk with neighboring including endothelial, glial, neuronal cells. Dysfunction contribute wide variety diseases lead cognitive impairments such as small disease (SVD), acute stroke, Alzheimer’s (AD), other neurological disorders. For instance, SVDs, pericyte degeneration leads microvessel instability demyelination while constriction after ischemia causes no-reflow phenomenon brain capillaries. AD, which shares some common risk factors dementia, reduction coverage subsequent microvascular observed association white matter attenuation impaired cognition. Pericyte loss BBB-breakdown, stagnates amyloid β leakage neurotoxic molecules into parenchyma. this review, we first summarize characteristics pericytes, their roles central nervous system. Then, focus on how dysfunctional pathogenesis impairment ‘small vessel’ ‘large diseases, well AD. Finally, discuss therapeutic implications for disorders by targeting pericytes.

Язык: Английский

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Reactive astrocytes: The nexus of pathological and clinical hallmarks of Alzheimer’s disease

Ageing Research Reviews, Год журнала: 2021, Номер 68, С. 101335 - 101335

Опубликована: Апрель 1, 2021

Astrocyte reactivity is a hallmark of neuroinflammation that arises with Alzheimer's disease (AD) and nearly every other neurodegenerative condition. While astrocytes certainly contribute to classic inflammatory processes (e.g. cytokine release, waste clearance, tissue repair), newly emerging technologies for measuring targeting cell specific activities in the brain have uncovered essential roles synapse function, metabolism, neurovascular coupling, sleep/wake patterns. In this review, we use holistic approach incorporate, expand upon, neuroinflammatory concepts consider how astrocyte dysfunction/reactivity modulates multiple pathological clinical hallmarks AD. Our ever-evolving understanding signaling neurodegeneration not only revealing new drug targets treatments dementia but suggesting reimagine AD pathophysiological mechanisms.

Язык: Английский

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Tumor-derived small extracellular vesicles in cancer invasion and metastasis: molecular mechanisms, and clinical significance

Molecular Cancer, Год журнала: 2024, Номер 23(1)

Опубликована: Янв. 19, 2024

Abstract The production and release of tumor-derived small extracellular vesicles (TDSEVs) from cancerous cells play a pivotal role in the propagation cancer, through genetic biological communication with healthy cells. TDSEVs are known to orchestrate invasion-metastasis cascade via diverse pathways. Regulation early metastasis processes, pre-metastatic niche formation, immune system regulation, angiogenesis initiation, matrix (ECM) remodeling, modulation, epithelial-mesenchymal transition (EMT) among pathways regulated by TDSEVs. MicroRNAs (miRs) carried within as double-edged sword can either promote or inhibit cancer progression. serve excellent markers for detection tumors, tumor metastases. From therapeutic point view, risk may be reduced limiting On other hand, represent promising approach vivo delivery cargo present review article discusses recent developments current views field research clinical applications.

Язык: Английский

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Precision drug delivery to the central nervous system using engineered nanoparticles

Nature Reviews Materials, Год журнала: 2024, Номер 9(8), С. 567 - 588

Опубликована: Июнь 25, 2024

Язык: Английский

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Revolutionizing Neurocare: Biomimetic Nanodelivery Via Cell Membranes

Advanced Materials, Год журнала: 2024, Номер 36(26)

Опубликована: Апрель 7, 2024

Abstract Brain disorders represent a significant challenge in medical science due to the formidable blood–brain barrier (BBB), which severely limits penetration of conventional therapeutics, hindering effective treatment strategies. This review delves into innovative realm biomimetic nanodelivery systems, including stem cell‐derived nanoghosts, tumor cell membrane‐coated nanoparticles, and erythrocyte membrane‐based carriers, highlighting their potential circumvent BBB's restrictions. By mimicking native properties, these nanocarriers emerge as promising solution for enhancing drug delivery brain, offering strategic advantage overcoming barrier's selective permeability. The unique benefits leveraging membranes from various sources is evaluated advanced technologies fabricating membrane‐encapsulated nanoparticles capable masquerading endogenous cells are examined. enables targeted broad spectrum therapeutic agents, ranging small molecule drugs proteins, thereby providing an approach neurocare. Further, contrasts capabilities limitations with traditional methods, underlining enable targeted, sustained, minimally invasive modalities. concluded perspective on clinical translation underscoring transformative impact landscape intractable brain diseases.

Язык: Английский

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The Crucial Role of the Blood–Brain Barrier in Neurodegenerative Diseases: Mechanisms of Disruption and Therapeutic Implications

Journal of Clinical Medicine, Год журнала: 2025, Номер 14(2), С. 386 - 386

Опубликована: Янв. 9, 2025

The blood-brain barrier (BBB) is a crucial structure that maintains brain homeostasis by regulating the entry of molecules and cells from bloodstream into central nervous system (CNS). Neurodegenerative diseases such as Alzheimer's Parkinson's disease, well ischemic stroke, compromise integrity BBB. This leads to increased permeability infiltration harmful substances, thereby accelerating neurodegeneration. In this review, we explore mechanisms underlying BBB disruption, including oxidative stress, neuroinflammation, vascular dysfunction, loss tight junction integrity, in patients with neurodegenerative diseases. We discuss how breakdown contributes neurotoxicity, abnormal accumulation pathological proteins, all which exacerbate neuronal damage facilitate disease progression. Furthermore, potential therapeutic strategies aimed at preserving or restoring function, anti-inflammatory treatments, antioxidant therapies, approaches enhance integrity. Given role neurodegeneration, maintaining its represents promising approach slow prevent progression

Язык: Английский

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The Neurovascular Unit: Effects of Brain Insults During the Perinatal Period

Frontiers in Neuroscience, Год журнала: 2020, Номер 13

Опубликована: Янв. 22, 2020

The neurovascular unit (NVU) is a relatively recent concept in neuroscience that broadly describes the relationship between brain cells and their blood vessels. NVU incorporates cellular extracellular components involved regulating cerebral flow blood-brain barrier function. within adult has attracted strong research interest its structure function well described, however, developing over fetal neonatal period remains much less known. One area of particular perinatal development impact known neuropathological insults on NVU. aim this review to synthesize existing literature describe brain, with emphasis exploring effects insults. Accordingly, brief overview provided, before discussion how may be affected by pathologies. We have focused around three common insults: prematurity, acute hypoxia, chronic hypoxia. A greater understanding processes affecting enable application targeted therapies, as providing useful basis for it expands further into area.

Язык: Английский

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