Molecular Motors in Blood–Brain Barrier Maintenance by Astrocytes DOI Creative Commons
Ana Filipa Sobral, Inês Costa, Vanessa Teixeira

et al.

Brain Sciences, Journal Year: 2025, Volume and Issue: 15(3), P. 279 - 279

Published: March 6, 2025

The blood–brain barrier (BBB) comprises distinct cell types, including endothelial cells, pericytes, and astrocytes, is essential for central nervous system (CNS) homeostasis by selectively regulating molecular transport maintaining integrity. In particular, astrocytes are BBB function, as they maintain integrity through their end-feet, which form a physical biochemical interface that enhances function selectivity. Moreover, secrete growth factors like vascular factor (VEGF) transforming factor-beta (TGF-β), regulate tight junction (TJ) proteins (e.g., claudins occludins) crucial limiting paracellular permeability. Molecular motors kinesins, dynein, myosins these astrocyte functions. By facilitating vesicular trafficking protein transport, various functions, of junctional to support integrity, the proper mitochondria localization within processes efficient energy supply, polarized distribution aquaporin (AQP)-4 at end-feet water across BBB, modulation neuroinflammatory responses. myosin modulate actomyosin dynamics process outgrowth, adhesion, migration, morphology, functional roles. Thus, motor dysregulation in can compromise increasing risk neurodegeneration. This review explores complex interplay between homeostasis, represents an attractive but poorly explored area research.

Language: Английский

Role of Microglia and Astrocytes in Alzheimer’s Disease: From Neuroinflammation to Ca2+ Homeostasis Dysregulation DOI Creative Commons
Giulia Di Benedetto, Chiara Burgaletto, Carlo Maria Bellanca

et al.

Cells, Journal Year: 2022, Volume and Issue: 11(17), P. 2728 - 2728

Published: Sept. 1, 2022

Alzheimer’s disease (AD) is the most common form of dementia worldwide, with a complex, poorly understood pathogenesis. Cerebral atrophy, amyloid-β (Aβ) plaques, and neurofibrillary tangles represent main pathological hallmarks AD brain. Recently, neuroinflammation has been recognized as prominent feature brain substantial evidence suggests that inflammatory response modulates progression. Additionally, dysregulation calcium (Ca2+) homeostasis represents another early factor involved in pathogenesis, intracellular Ca2+ concentration essential to ensure proper cellular neuronal functions. Although growing supports involvement mechanisms neurodegeneration-related processes, scant data are available on its contribution microglia astrocytes functioning, both health throughout continuum. Nevertheless, AD-related aberrant signalling crucially underpinning neuroinflammatory processes that, turn, impact function. In this light, we attempted provide an overview current understanding interactions between glia cells-mediated responses molecular AD.

Language: Английский

Citations

89
Neural stem cell-derived exosomes and regeneration: cell-free therapeutic strategies for traumatic brain injury DOI Creative Commons
Lin Zhong, Jingjing Wang, Peng Wang

et al.

Stem Cell Research & Therapy, Journal Year: 2023, Volume and Issue: 14(1)

Published: Aug. 8, 2023

Abstract Regenerative repair of the brain after traumatic injury (TBI) remains an extensive clinical challenge, inspiring intensified interest in therapeutic approaches to explore superior strategies. Exosome therapy is another research hotspot following stem cell alternative therapy. Prior verified that exosomes produced by neural cells can participate physiological and pathological changes associated with TBI have potential neuroregulatory functions. In comparison their parental cells, stability immune tolerance lower tumorigenic risk. addition, they readily penetrate blood‒brain barrier, which makes treatment efficiency transplanted cells. Exosomes secreted present a promising strategy for development novel regenerative therapies. Their tissue regeneration immunomodulatory made them encouraging candidates repair. The review addresses challenges, applications mechanisms regenerating damaged brains.

Language: Английский

Citations

50
Astrocyte Involvement in Blood–Brain Barrier Function: A Critical Update Highlighting Novel, Complex, Neurovascular Interactions DOI Open Access
Doina Manu, Mark Slevin, Laura Bărcuțean

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(24), P. 17146 - 17146

Published: Dec. 5, 2023

Neurological disorders have been linked to a defective blood–brain barrier (BBB), with dysfunctions triggered by stage-specific disease mechanisms, some of these being generated through interactions in the neurovascular unit (NVU). Advanced knowledge molecular and signaling mechanisms NVU emergence improved experimental models allow BBB permeability prediction development new brain-targeted therapies. As constituents, astrocytes are most numerous glial cells, characterized heterogeneity that occurs as result developmental context-based gene expression profiles differential non-coding ribonucleic acids (RNAs). Due their dynamic responses different signals, may beneficial or detrimental role BBB’s function, deep effects on pathophysiology (and progression of) central nervous system diseases. The implication astrocytic-derived extracellular vesicles pathological due ability pass BBB, must also be considered. astrocytes’ interaction endothelial cells at level considered promising therapeutic targets neurological conditions. Nevertheless, personalized well-founded approach addressed, temporal spatial reactive astrogliosis states during disease.

Language: Английский

Citations

45
The Crucial Role of the Blood–Brain Barrier in Neurodegenerative Diseases: Mechanisms of Disruption and Therapeutic Implications DOI Open Access
Sehwan Kim, Un Ju Jung, Sang Ryong Kim

et al.

Journal of Clinical Medicine, Journal Year: 2025, Volume and Issue: 14(2), P. 386 - 386

Published: Jan. 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

Language: Английский

Citations

5
Understanding glucose metabolism and insulin action at the blood–brain barrier: Implications for brain health and neurodegenerative diseases DOI Creative Commons

Yiyi Zhu,

Alexei Verkhratsky, Hui Chen

et al.

Acta Physiologica, Journal Year: 2025, Volume and Issue: 241(2)

Published: Jan. 16, 2025

The blood-brain barrier (BBB) is a highly selective, semipermeable critical for maintaining brain homeostasis. BBB regulates the transport of essential nutrients, hormones, and signaling molecules between bloodstream central nervous system (CNS), while simultaneously protecting from potentially harmful substances pathogens. This selective permeability ensures that nourished shielded toxins. An exception to this are regions, such as hypothalamus circumventricular organs, which irrigated by fenestrated capillaries, allowing rapid direct response various blood components. We overview metabolic functions BBB, with an emphasis on impact altered glucose metabolism insulin in pathogenesis neurodegenerative diseases. Notably, endothelial cells constituting exhibit distinct characteristics, primarily generating ATP through aerobic glycolysis. occurs despite their exposure abundant oxygen bloodstream, typically supports oxidative phosphorylation. effects astrocytes, form glial limitans component show marked sexual dimorphism. nutrient sensing hypothalamus, along signaling, systemic metabolism. Insulin modifies regulating expression tight junction proteins, angiogenesis, vascular remodeling, well modulating flow brain. disruptions particularly evident diseases, Alzheimer's disease Parkinson's disease, where breakdown accelerates cognitive decline. review highlights role normal functionality investigates how these pathways contribute onset progression

Language: Английский

Citations

5
Neuroglial decline defines cognitive ageing DOI Creative Commons
Alexei Verkhratsky

Ageing & Longevity, Journal Year: 2025, Volume and Issue: 1.2025, P. 6 - 21

Published: Jan. 17, 2025

Neuroglia of the central nervous system, represented by astroglia, oligodendroglia and microglia, are fundamental for life-long support homeostasis, plasticity defence neural tissue. In particular neuroglial cells contribute to cognitive reserve, which defines neurological outcome both physiological pathological ageing. Physiological ageing is accompanied with structural functional decline neuroglia. particular, astrocytes undergo morphological atrophy asthenia compromises their vital functions such as glutamate clearance, K+ buffering synaptic support. Old oligodendrocytes lose myelination capacity, results in thinning myelin sheath white matter. Finally, associated accumulation dystrophic microglia limits neuroprotection. Age-dependent impedes contributes impairment, increases vulnerability system neurodegeneration. Life style changes positively impact on structure function this improving longevity. Keywords: ageing; longevity; neuroglia, oligodendroglia; oligodendroglial precursor cells;

Language: Английский

Citations

3
Astroglia support, regulate and reinforce brain barriers DOI Creative Commons
Alexei Verkhratsky, Augustas Pivoriūnas

Neurobiology of Disease, Journal Year: 2023, Volume and Issue: 179, P. 106054 - 106054

Published: Feb. 25, 2023

Nervous system is segregated from the body by complex of barriers. The CNS protected (i) blood–brain and blood-spinal cord barrier between intracerebral intraspinal blood vessels brain parenchyma; (ii) arachnoid blood-cerebrospinal fluid barrier; (iii) circumventricular organs made tanycytes (iv) choroid plexus blood-CSF formed ependymocytes. In peripheral nervous nerve-blood secured tight junctions specialised glial cells known as perineural cells. astroglia contribute to all barriers through glia limitans, which represent parenchymal portion system. Astroglia secretion various paracrine factors regulate permeability endothelial vascular in pathology damage or asthenia astrocytes may compromise integrity.

Language: Английский

Citations

29
The gut microbiota‐astrocyte axis: Implications for type 2 diabetic cognitive dysfunction DOI Creative Commons
Zi-han Li, Yayi Jiang,

Caiyi Long

et al.

CNS Neuroscience & Therapeutics, Journal Year: 2023, Volume and Issue: 29(S1), P. 59 - 73

Published: Jan. 4, 2023

Abstract Background Diabetic cognitive dysfunction (DCD) is one of the most insidious complications type 2 diabetes mellitus, which can seriously affect ability to self‐monitoring blood glucose and quality life in elderly. Previous pathological studies have focused on neuronal dysfunction, characterized by extracellular beta‐amyloid deposition intracellular tau hyperphosphorylation. In recent years, astrocytes been recognized as a potential therapeutic target for important participants central control metabolism. The disorder gut microbiota their metabolites linked series metabolic diseases such mellitus. imbalance intestinal flora has effect promoting occurrence deterioration several diabetes‐related complications. Gut microbes drive astrocyte activation. Aims We reviewed progress DCD related “gut microbiota‐astrocyte” axis terms peripheral inflammation, blood–brain barrier (BBB) systemic brain energy metabolism disorders deepen research explore targets. Conclusion “Gut axis, unique bidirectional crosstalk brain‐gut mediates intermediate process neurocognitive secondary

Language: Английский

Citations

28
Crosstalk of Astrocytes and Other Cells during Ischemic Stroke DOI Creative Commons
Tingting He, Guo‐Yuan Yang,

Zhijun Zhang

et al.

Life, Journal Year: 2022, Volume and Issue: 12(6), P. 910 - 910

Published: June 17, 2022

Stroke is a leading cause of death and long-term disability worldwide. Astrocytes structurally compose tripartite synapses, blood–brain barrier, the neurovascular unit perform multiple functions through cell-to-cell signaling neurons, glial cells, vasculature. The crosstalk astrocytes other cells complicated incompletely understood. Here we review role in response to ischemic stroke, both beneficial detrimental, from cell–cell interaction perspective. Reactive provide neuroprotection antioxidation antiexcitatory effects metabolic support; they also contribute neurorestoration involving neurogenesis, synaptogenesis, angiogenesis, oligodendrogenesis by with stem cell lineage. In meantime, reactive play vital neuroinflammation brain edema. Glial scar formation chronic phase hinders functional recovery. We further discuss astrocyte enriched microRNAs exosomes regulation stroke. addition, latest notion subsets astrocytic activity revealed optogenetics mentioned. This discusses current understanding intimate molecular conversation between outlines its potential implications after “Neurocentric” strategies may not be sufficient for neurological protection recovery; future therapeutic could target astrocytes.

Language: Английский

Citations

39
Astroglial functions DOI Creative Commons
Alexei Verkhratsky, Arthur M. Butt

Neuroglia, Journal Year: 2023, Volume and Issue: unknown, P. 199 - 294

Published: Jan. 1, 2023

Astroglial cells are fundamental for the most basic functions of central nervous system, which define its development, maintenance, survival and operation. Astroglia key element brain barriers, production turnover cerebrospinal fluid, ionostasis extracellular space. Astrocytes maintain function glymphatic system responsible from removal cellular waste. an indispensable part synaptic networks, controlling synaptogenesis, maintenance elimination, through astroglial cradle. Finally, astrocytic morphological functional plasticity critical elements plastic remodelling neuronal ensembles, this being learning, memory behaviour.

Language: Английский

Citations

19