What is a cell type and how to define it?

Cell, Год журнала: 2022, Номер 185(15), С. 2739 - 2755

Опубликована: Июль 1, 2022

Язык: Английский

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Oxidative stress and impaired oligodendrocyte precursor cell differentiation in neurological disorders

Cellular and Molecular Life Sciences, Год журнала: 2021, Номер 78(10), С. 4615 - 4637

Опубликована: Март 10, 2021

Oligodendrocyte precursor cells (OPCs) account for 5% of the resident parenchymal central nervous system glial cells. OPCs are not only a back-up loss oligodendrocytes that occurs due to brain injury or inflammation-induced demyelination (remyelination) but also pivotal in plastic processes such as learning and memory (adaptive myelination). OPC differentiation into mature myelinating is controlled by complex transcriptional network depends on high metabolic mitochondrial demand. Mounting evidence shows dysfunction, culminating lack differentiation, mediates progression neurodegenerative disorders multiple sclerosis, Alzheimer's disease Parkinson's disease. Importantly, neurodegeneration characterised oxidative carbonyl stress, which may primarily affect plasticity demand limited antioxidant capacity associated with this cell type. The underlying mechanisms how oxidative/carbonyl stress disrupt remain enigmatic focus current research efforts. This review proposes role interfering changes required differentiation. In particular, oligodendrocyte (epi)genetics, cellular defence repair responses, signalling respiration, lipid metabolism represent key hamper disorders. Understanding impacts function pave way future OPC-targeted treatment strategies

Язык: Английский

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Neurovascular Unit: A critical role in ischemic stroke

CNS Neuroscience & Therapeutics, Год журнала: 2021, Номер 27(1), С. 7 - 16

Опубликована: Янв. 1, 2021

Abstract Ischemic stroke (IS), a common cerebrovascular disease, results from sudden blockage of blood vessel in the brain, thereby restricting supply to area question, and making significantly negative impact on human health. Unfortunately, current treatments, that are mainly based recanalization occluded vessels, insufficient or inaccessible many patients. Recently, profound influence neurovascular unit (NVU) prognosis IS have become better understood; in‐depth studies NVU also provided novel approaches for treatment. In this article, we review intimate connections between changes outcomes, discuss possible new management strategies having practical significance IS. We concept NVU, as well its roles blood‐brain barrier regulation, cell preservation, inflammatory immune response, repair. Besides, summarize noncoding RNAs therapies targeting NVU. conclude both pathophysiological repair processes strongly associated with homeostatic state further research into directed at could expand range treatments available

Язык: Английский

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Neuroinflammation in Vascular Cognitive Impairment and Dementia: Current Evidence, Advances, and Prospects

International Journal of Molecular Sciences, Год журнала: 2022, Номер 23(11), С. 6224 - 6224

Опубликована: Июнь 2, 2022

Vascular cognitive impairment and dementia (VCID) is a major heterogeneous brain disease caused by multiple factors, it the second most common type of in world. It long-term chronic low perfusion whole or local area, eventually develops into severe dysfunction syndrome. Because disease's ambiguous classification diagnostic criteria, there no clear treatment strategy for VCID, association between cerebrovascular pathology controversial. Neuroinflammation an immunological cascade reaction mediated glial cells central nervous system where innate immunity resides. Inflammatory reactions could be triggered various damaging events, including hypoxia, ischemia, infection. Long-term hypoperfusion-induced ischemia hypoxia can overactivate neuroinflammation, causing apoptosis, blood-brain barrier damage other pathological changes, triggering aggravating occurrence development VCID. In this review, we will explore mechanisms neuroinflammation induced hypoperfusion emphasize important role VCID from perspective immune cells, mediators signaling pathways, so as to provide valuable ideas prevention disease.

Язык: Английский

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Neuroinflammation, memory, and depression: new approaches to hippocampal neurogenesis

Journal of Neuroinflammation, Год журнала: 2023, Номер 20(1)

Опубликована: Ноя. 27, 2023

As one of most common and severe mental disorders, major depressive disorder (MDD) significantly increases the risks premature death other medical conditions for patients. Neuroinflammation is abnormal immune response in brain, its correlation with MDD receiving increasing attention. has been reported to be involved through distinct neurobiological mechanisms, among which dysregulation neurogenesis dentate gyrus (DG) hippocampus (HPC) The DG two niches adult mammalian neurotrophic factors are fundamental regulators this process. cell types mediating neuroinflammation include microglia, astrocytes, oligodendrocytes, meningeal leukocytes, peripheral cells selectively penetrate blood-brain barrier infiltrate into inflammatory regions. This review summarizes functions affected by during progression corresponding influences on memory patients model animals.

Язык: Английский

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Alterations of Oligodendrocyte and Myelin Energy Metabolism in Multiple Sclerosis

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(16), С. 12912 - 12912

Опубликована: Авг. 18, 2023

Multiple sclerosis (MS) is a complex autoimmune disease of the central nervous system (CNS), characterized by demyelination and neurodegeneration. Oligodendrocytes play vital role in maintaining integrity myelin, protective sheath around nerve fibres essential for efficient signal transmission. However, MS, oligodendrocytes become dysfunctional, leading to myelin damage axonal degeneration. Emerging evidence suggests that metabolic changes, including mitochondrial dysfunction alterations glucose lipid metabolism, contribute significantly pathogenesis MS. Mitochondrial observed both immune cells within CNS MS patients. Impaired function leads energy deficits, affecting crucial processes such as impulse transmission transport, ultimately contributing Moreover, linked generation reactive oxygen species (ROS), exacerbating inflammation. Altered metabolism affects supply required oligodendrocyte synthesis. Dysregulated results changes composition its stability integrity. Importantly, low levels polyunsaturated fatty acids are associated with upregulated enhanced catabolism. Understanding intricate relationship between these mechanisms developing targeted therapies preserve promote neurological recovery individuals Addressing aspects may offer new insights into potential therapeutic strategies halt progression improve quality life

Язык: Английский

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Genetic architecture of the structural connectome

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Март 4, 2024

Abstract Myelinated axons form long-range connections that enable rapid communication between distant brain regions, but how genetics governs the strength and organization of these remains unclear. We perform genome-wide association studies 206 structural connectivity measures derived from diffusion magnetic resonance imaging tractography 26,333 UK Biobank participants, each representing density myelinated within or a pair cortical networks, subcortical structures hemispheres. identify 30 independent significant variants after Bonferroni correction for number studied (126 at nominal significance) implicating genes involved in myelination ( SEMA3A ), neurite elongation guidance NUAK1 , STRN DPYSL2 EPHA3 HGF SHTN1 neural cell proliferation differentiation GMNC CELF4 neuronal migration CCDC88C cytoskeletal CTTNBP2 MAPT DAAM1 MYO16 PLEC metal transport SLC39A8 ). These have four broad patterns spatial with connectivity: some disproportionately strong associations corticothalamic connectivity, interhemispheric both, while others are more spatially diffuse. Structural highly polygenic, median 9.1 percent common estimated to non-zero effects on measure, exhibited signatures negative selection. genetic correlations variety neuropsychiatric cognitive traits, indicating connectivity-altering tend influence health function. Heritability is enriched regions increased chromatin accessibility adult oligodendrocytes (as well as microglia, inhibitory neurons astrocytes) multiple fetal types, suggesting control partially mediated by early development. Our results indicate pervasive, pleiotropic, structured white-matter via diverse neurodevelopmental pathways, support relevance this healthy

Язык: Английский

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Brain-targeted drug delivery - nanovesicles directed to specific brain cells by brain-targeting ligands

Journal of Nanobiotechnology, Год журнала: 2024, Номер 22(1)

Опубликована: Май 17, 2024

Abstract Neurodegenerative diseases are characterized by extensive loss of function or death brain cells, hampering the life quality patients. Brain-targeted drug delivery is challenging, with a low success rate this far. Therefore, application targeting ligands in vehicles, such as lipid-based and polymeric nanoparticles, holds promise to overcome blood-brain barrier (BBB) direct therapies brain, addition protect their cargo from degradation metabolization. In review, we discuss barriers different types brain-targeting currently use brain-targeted peptides, proteins, aptamers, small molecules, antibodies. Moreover, present detailed review used nanoparticles specific like neurons (C4-3 aptamer, neurotensin, Tet-1, RVG, IKRG peptides), astrocytes (Aquaporin-4, D4, Bradykinin B2 antibodies), oligodendrocytes (NG-2 antibody biotinylated DNA aptamer conjugated streptavidin core Myaptavin-3064), microglia (CD11b antibody), neural stem cells (QTRFLLH, VPTQSSG, NFL-TBS.40–63 endothelial BBB (transferrin insulin choline). Reports demonstrated enhanced improved transport cell type targeted conjugation these nanoparticles. Hence, strategy allows implementation high-precision medicine, reduced side effects unwanted therapy clearance body. Nevertheless, accumulation some peripheral organs has been reported indicating that there still factors be achieve higher levels targeting. This collection studies exploring for highlight advantages limitations approach precision therapies.

Язык: Английский

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AAV Targeting of Glial Cell Types in the Central and Peripheral Nervous System and Relevance to Human Gene Therapy

Frontiers in Molecular Neuroscience, Год журнала: 2021, Номер 13

Опубликована: Янв. 11, 2021

Different glial cell types are found throughout the central (CNS) and peripheral nervous system (PNS), where they have important functions. These also involved in pathology, playing roles neurodegenerative disease following trauma brain spinal cord (astrocytes, microglia, oligodendrocytes), nerve degeneration development of pain nerves (Schwann cells, satellite cells), retinal diseases (Müller glia) gut dysbiosis (enteric glia). type all been proposed as potential targets for treating these conditions. One approach to target is use gene therapy modify expression. Adeno-associated virus (AAV) vectors shown be safe effective targeting cells used a number clinical trials. To date, studies tested different AAV serotypes cell-specific promoters increase tropism However, true glial-cell specific particular remains elusive. This review provides an overview research into developing discusses some issues that still need addressed make reality.

Язык: Английский

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Neurobiology of cannabinoid receptor signaling

Dialogues in Clinical Neuroscience, Год журнала: 2020, Номер 22(3), С. 207 - 222

Опубликована: Сен. 30, 2020

The endocannabinoid system (ECS) is a highly versatile signaling within the nervous system. Despite its widespread localization, functions context of distinct neural processes are very well discernable and specific. This remarkable, question remains as to how such specificity achieved. One key player in ECS cannabinoid type 1 receptor (CB1), G protein–coupled characterized by complexity cell-specific expression, cellular subcellular adaptable regulation intracellular cascades. CB1 receptors involved different synaptic plasticity brain's bioenergetics context-specific manner. CB2 also important several neurons, glial cells, immune cells brain. As polymorphisms components, external impacts stress metabolic challenges, can both lead dysregulated activity subsequently possible neuropsychiatric disorders, pharmacological intervention targeting promising therapeutic approach. Understanding neurobiology depth will aid optimal design interventions, minimizing unwanted side effects.

Язык: Английский

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