The role of extracellular vesicles in the physiological and pathological regulation of the blood–brain barrier

FASEB BioAdvances, Год журнала: 2021, Номер 3(9), С. 665 - 675

Опубликована: Июль 7, 2021

Extracellular vesicles (EVs) are a subclass of biological nanoparticles secreted by most cell types. Once secreted, EVs can travel long distances to deliver their content target cells thereby playing key role in cell-to-cell communication and supporting both physiological pathological processes. In recent years, the functional versatility has come be more widely appreciated. Their heterogeneous structure encloses solubilized bioactive cargoes including proteins nucleic acids. mirror secreting composition therefore representing novel source diagnostic prognostic biomarkers. Moreover, due unique structure, constitute promising class biocompatible nanovehicles for drug delivery as well. Importantly, burgeoning interest, is fact that have intrinsic ability breach barriers complex blood-brain barrier (BBB), whose restrictive nature represents significant therapeutic challenge. been shown contribute progression variety brain diseases metastatic cancer, neurodegenerative diseases, acute pathologies infections ischemia. this review, maintenance regulation BBB under normal pathologic conditions discussed. Applications tools treatment affect central nervous system presented limitations hindering broad translation potential solutions resolve them.

Язык: Английский

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Biomarkers of Neurodegenerative Diseases: Biology, Taxonomy, Clinical Relevance, and Current Research Status

Biomedicines, Год журнала: 2022, Номер 10(7), С. 1760 - 1760

Опубликована: Июль 21, 2022

The understanding of neurodegenerative diseases, traditionally considered to be well-defined entities with distinguishable clinical phenotypes, has undergone a major shift over the last 20 years. diagnosis diseases primarily requires functional brain imaging techniques or invasive tests such as lumbar puncture assess cerebrospinal fluid. A new biological approach and research efforts, especially in vivo, have focused on biomarkers indicating underlying proteinopathy fluid blood serum. However, due complexity heterogeneity processes within central nervous system large number overlapping diagnoses, identifying individual proteinopathies is relatively difficult often not entirely accurate. For this reason, there an urgent need develop laboratory methods for specific biomarkers, understand molecular basis disorders classify quantifiable readily available tools that can accelerate efforts translate knowledge into disease-modifying therapies improve simplify areas differential diagnosis, well monitor disease course aim estimating prognosis evaluating effects treatment. review summarize current about clinically relevant different diseases.

Язык: Английский

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Extracellular vesicles, the emerging mirrors of brain physiopathology

International Journal of Biological Sciences, Год журнала: 2023, Номер 19(3), С. 721 - 743

Опубликована: Янв. 1, 2023

Extracellular vesicles are secreted by a wide variety of cells, and their primary functions include intercellular communication, immune responses, human reproduction, synaptic plasticity.Their molecular cargo reflects the physiological processes that cells origin undergoing.Thus, many studies have suggested extracellular could be promising biomarker tool for diseases, mainly due to biological relevance easy accessibility broad range body fluids.Moreover, since composition leads them cross blood-brain barrier bidirectionally, growing evidence points as emerging mirrors brain diseases processes.In this regard, review explores biogenesis vesicles, role in different pathological processes, potential clinical practice, recent outstanding about exosomes major such Alzheimer's disease (AD), Parkinson's (PD), multiple sclerosis (MS), amyotrophic lateral (ALS), or tumors.

Язык: Английский

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The Roles of Exosomal Proteins: Classification, Function, and Applications

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(4), С. 3061 - 3061

Опубликована: Фев. 4, 2023

Exosome, a subpopulation of extracellular vesicles, plays diverse roles in various biological processes. As one the most abundant components exosomes, exosomal proteins have been revealed to participate development many diseases, such as carcinoma, sarcoma, melanoma, neurological disorders, immune responses, cardiovascular and infection. Thus, understanding functions mechanisms potentially assists clinical diagnosis targeted delivery therapies. However, current knowledge about function application is still limited. In this review, we summarize classification proteins, exosome biogenesis disease development, well applications.

Язык: Английский

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Exosomes in brain diseases: Pathogenesis and therapeutic targets

MedComm, Год журнала: 2023, Номер 4(3)

Опубликована: Июнь 1, 2023

Exosomes are extracellular vesicles with diameters of about 100 nm that naturally secreted by cells into body fluids. They derived from endosomes and wrapped in lipid membranes. involved intracellular metabolism intercellular communication. contain nucleic acids, proteins, lipids, metabolites the cell microenvironment cytoplasm. The contents exosomes can reflect their cells' origin allow observation tissue changes states under disease conditions. Naturally have specific biomolecules act as "fingerprint" parent cells, changed pathological conditions be used biomarkers for diagnosis. low immunogenicity, small size, cross blood-brain barrier. These characteristics make unique engineering carriers. incorporate therapeutic drugs achieve targeted drug delivery. carriers therapy still infancy, but exosome provides a new perspective cell-free therapy. This review discussed relationship occurrence treatment some neuropsychiatric diseases. In addition, future applications diagnosis disorders were evaluated this review.

Язык: Английский

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Poly (ADP-Ribose) polymerase 1 and parthanatos in neurological diseases: From pathogenesis to therapeutic opportunities

Neurobiology of Disease, Год журнала: 2023, Номер 187, С. 106314 - 106314

Опубликована: Окт. 1, 2023

Poly (ADP-ribose) polymerase-1 (PARP-1) is the most extensively studied member of PARP superfamily, with its primary function being facilitation DNA damage repair processes. Parthanatos a type regulated cell death cascade initiated by PARP-1 hyperactivation, which involves multiple subroutines, including accumulation ADP-ribose polymers (PAR), binding PAR and apoptosis-inducing factor (AIF), release AIF from mitochondria, translocation AIF/macrophage migration inhibitory (MIF) complex, massive MIF-mediated fragmentation. Over past few decades, role in central nervous system health disease has received increasing attention. In this review, we discuss biological functions neural proliferation differentiation, memory formation, brain ageing, epigenetic regulation. We then elaborate on involvement PARP-1-dependant parthanatos various neuropathological processes, such as oxidative stress, neuroinflammation, mitochondrial dysfunction, excitotoxicity, autophagy damage, endoplasmic reticulum (ER) stress. Additional highlight contains PARP-1's implications initiation, progression, therapeutic opportunities for different neurological illnesses, neurodegenerative diseases, stroke, autism spectrum disorder (ASD), sclerosis (MS), epilepsy, neuropathic pain (NP). Finally, emerging insights into repurposing inhibitors management diseases are provided. This review aims to summarize exciting advancements critical disorders, may open new avenues options targeting or parthanatos.

Язык: Английский

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C1q is increased in cerebrospinal fluid‐derived extracellular vesicles in Alzheimer's disease: A multi‐cohort proteomics and immuno‐assay validation study

Alzheimer s & Dementia, Год журнала: 2023, Номер 19(11), С. 4828 - 4840

Опубликована: Апрель 6, 2023

Abstract Introduction Extracellular vesicles (EVs) may propagate and modulate Alzheimer's disease (AD) pathology. We aimed to comprehensively characterize the proteome of cerebrospinal fluid (CSF) EVs identify proteins pathways altered in AD. Methods CSF were isolated by ultracentrifugation (Cohort 1) or Vn96 peptide 2) from non‐neurodegenerative controls ( n = 15, 16) AD patients 22, 20, respectively). subjected untargeted quantitative mass spectrometry‐based proteomics. Results validated enzyme‐linked immunosorbent assay (ELISA) Cohorts 3 4, consisting 16, 43, (Cohort3, Cohort4)), with 24, 100). found > 30 differentially expressed involved immune‐regulation. Increase C1q levels compared non‐demented was ELISA (∼ 1.5 fold, p 3) 0.03, 4) 0.005). Discussion be utilized as a potential biomarker play so far unprecedented role immune‐regulation

Язык: Английский

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Exosomes-Based Nanomedicine for Neurodegenerative Diseases: Current Insights and Future Challenges

Pharmaceutics, Год журнала: 2023, Номер 15(1), С. 298 - 298

Опубликована: Янв. 16, 2023

Neurodegenerative diseases constitute a group of pathologies whose etiology remains unknown in many cases, and there are no treatments that stop the progression such diseases. Moreover, existence blood–brain barrier is an impediment to penetration exogenous molecules, including those found drugs. Exosomes extracellular vesicles secreted by wide variety cells, their primary functions include intercellular communication, immune responses, human reproduction, synaptic plasticity. Due natural origin molecular similarities with most cell types, exosomes have emerged as promising therapeutic tools for numerous Specifically, neurodegenerative shown be potential target this nanomedicine strategy due difficult access brain strategy’s pathophysiological complexity. In regard, review explores important biological-origin drug delivery systems, innovative isolation methods exosomes, physicochemical characterization, loading, cutting-edge functionalization strategies them within brain, latest research studies diseases, future challenges nanomedicine-based tools.

Язык: Английский

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Extracellular Vesicles as Potential Biomarkers in Amyotrophic Lateral Sclerosis

Genes, Год журнала: 2023, Номер 14(2), С. 325 - 325

Опубликована: Янв. 27, 2023

Amyotrophic lateral sclerosis (ALS) is described as a fatal and rapidly progressive neurodegenerative disorder caused by the degeneration of upper motor neurons in primary cortex lower brainstem spinal cord. Due to ALS’s slowly characteristic, which often accompanied other neurological comorbidities, its diagnosis remains challenging. Perturbations vesicle-mediated transport autophagy well cell-autonomous disease initiation glutamatergic have been revealed ALS. The use extracellular vesicles (EVs) may be key accessing pathologically relevant tissues for ALS, EVs can cross blood–brain barrier isolated from blood. number content provide indications pathogenesis, stage, prognosis. In this review, we collected recent study aiming at identification biomarker ALS with respect size, quantity, biological fluids patients compared controls.

Язык: Английский

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Central nervous system-derived extracellular vesicles: the next generation of neural circulating biomarkers?

Translational Neurodegeneration, Год журнала: 2024, Номер 13(1)

Опубликована: Июнь 19, 2024

Abstract The central nervous system (CNS) is integrated by glial and neuronal cells, both release extracellular vesicles (EVs) that participate in CNS homeostasis. EVs could be one of the best candidates to operate as nanosized biological platforms for analysing multidimensional bioactive cargos, which are protected during systemic circulation EVs. Having a window into molecular level processes happening open new avenue research. This raises particular point interest: can CNS-derived blood serve circulating biomarkers reflect pathological status neurological diseases? L1 cell adhesion molecule (L1CAM) widely reported biomarker identify peripheral blood. However, it has been demonstrated L1CAM also expressed outside CNS. Given principal data related neurodegenerative diseases, such multiple sclerosis, amyotrophic lateral Parkinson’s disease Alzheimer’s were obtained using L1CAM-positive EVs, efforts overcome present challenges its specificity required. In this sense, other surface glutamate aspartate transporter (GLAST) myelin oligodendrocyte glycoprotein (MOG), among others, have started used. Establishing panel EV analyse increase sensitivity necessary these types studies. review covers main evidence cerebrospinal fluid samples patients with focusing on technical possibilities their isolation. emerging mirror brain physiopathology, reflecting localized changes. Therefore, when hindrances research clinical applications overcome, novel disease-specific panels would discovered facilitate transformation from traditional medicine personalized medicine.

Язык: Английский

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