Roles of vimentin in health and disease

Genes & Development, Journal Year: 2022, Volume and Issue: 36(7-8), P. 391 - 407

Published: April 1, 2022

More than 27 yr ago, the vimentin knockout ( Vim −/− ) mouse was reported to develop and reproduce without an obvious phenotype, implying that this major cytoskeletal protein nonessential. Subsequently, comprehensive careful analyses have revealed numerous phenotypes in mice their organs, tissues, cells, frequently reflecting altered responses recovery of tissues following various insults or injuries. These findings been supported by cell-based experiments demonstrating intermediate filaments (IFs) play a critical role regulating cell mechanics are required coordinate mechanosensing, transduction, signaling pathways, motility, inflammatory responses. This review highlights essential functions IFs from studies cells derived them.

Language: Английский

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Astrocytes in human central nervous system diseases: a frontier for new therapies

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: Oct. 13, 2023

Astroglia are a broad class of neural parenchymal cells primarily dedicated to homoeostasis and defence the central nervous system (CNS). contribute pathophysiology all neurological neuropsychiatric disorders in ways that can be either beneficial or detrimental disorder outcome. Pathophysiological changes astroglia primary secondary result gain loss functions. respond external, non-cell autonomous signals associated with any form CNS pathology by undergoing complex variable their structure, molecular expression, function. In addition, internally driven, cell astroglial innate properties lead pathologies. Astroglial is complex, different pathophysiological states phenotypes context-specific vary disorder, disorder-stage, comorbidities, age, sex. Here, we classify into (i) reactive astrogliosis, (ii) atrophy function, (iii) degeneration death, (iv) astrocytopathies characterised aberrant forms drive disease. We review across spectrum human diseases disorders, including neurotrauma, stroke, neuroinfection, autoimmune attack epilepsy, as well neurodevelopmental, neurodegenerative, metabolic disorders. Characterising cellular mechanisms represents new frontier identify novel therapeutic strategies.

Language: Английский

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Unveiling the role of astrocytes in postoperative cognitive dysfunction

Ageing Research Reviews, Journal Year: 2024, Volume and Issue: 95, P. 102223 - 102223

Published: Feb. 5, 2024

Language: Английский

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TGF-β as a Key Modulator of Astrocyte Reactivity: Disease Relevance and Therapeutic Implications

Biomedicines, Journal Year: 2022, Volume and Issue: 10(5), P. 1206 - 1206

Published: May 23, 2022

Astrocytes are essential for normal brain development and functioning. They respond to injury disease through a process referred as reactive astrogliosis, where the reactivity is highly heterogenous context-dependent. Reactive astrocytes active contributors pathology can exert beneficial, detrimental, or mixed effects following insults. Transforming growth factor-β (TGF-β) has been identified one of key factors regulating astrocyte reactivity. The genetic pharmacological manipulation TGF-β signaling pathway in animal models central nervous system (CNS) alters pathological functional outcomes. This review aims provide recent understanding regarding injury, aging, neurodegeneration. Further, it explores how modulates function context CNS injury.

Language: Английский

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Vimentin as a potential target for diverse nervous system diseases

Neural Regeneration Research, Journal Year: 2022, Volume and Issue: 18(5), P. 969 - 969

Published: Oct. 27, 2022

Vimentin is a major type III intermediate filament protein that plays important roles in several basic cellular functions including cell migration, proliferation, and division. Although vimentin cytoplasmic protein, it also exists the extracellular matrix at surface. Previous studies have shown may exert multiple physiological effects different nervous system injuries diseases. For example, of spinal cord injury stroke mainly focus on formation reactive astrocytes. Reduced glial scar, increased axonal regeneration, improved motor function been noted after fibrillary acidic knockout (GFAP-/-VIM-/-) mice. However, attenuated scar post-stroke GFAP-/- VIM-/- mice resulted abnormal neuronal network restoration worse neurological recovery. These opposite results attributed to temporal spatial conditions. In addition, be neurotrophic factor promotes extension by interaction with insulin-like growth 1 receptor. pathogenesis bacterial meningitis, surface meningitis facilitator, acting as receptor pathogenic bacteria, E. coli K1, Listeria monocytogenes, group B streptococcus. Compared wild mice, are less susceptible infection exhibit reduced inflammatory response, suggesting necessary induce meningitis. Recently published literature showed serves double-edged sword system, regulating regrowth, myelination, apoptosis, neuroinflammation. This review aims provide an overview injury, stroke, gliomas, peripheral nerve discuss potential therapeutic methods involving manipulation improving alleviating infection, inhibiting brain tumor progression, enhancing myelination.

Language: Английский

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Complement C3a treatment accelerates recovery after stroke via modulation of astrocyte reactivity and cortical connectivity

Journal of Clinical Investigation, Journal Year: 2023, Volume and Issue: 133(10)

Published: March 30, 2023

Despite advances in acute care, ischemic stroke remains a major cause of long-term disability. Approaches targeting both neuronal and glial responses are needed to enhance recovery improve outcome. The complement C3a receptor (C3aR) is regulator inflammation with roles neurodevelopment, neural plasticity, neurodegeneration. Using mice lacking C3aR (C3aR-/-) overexpressing the brain, we uncovered 2 opposing effects signaling on functional after stroke: inhibition phase facilitation later phase. Peri-infarct astrocyte reactivity was increased density microglia reduced C3aR-/- mice; overexpression led opposite effects. Pharmacological treatment wild-type intranasal starting 7 days accelerated motor function attenuated without enhancing microgliosis. stimulated global white matter reorganization, peri-infarct structural connectivity, upregulated Igf1 Thbs4 cortex. Thus, from day exerts positive astrocytes connectivity while avoiding deleterious consequences during Intranasal administration agonists within convenient time window holds translational promise outcome stroke.

Language: Английский

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Neurorestorative Approaches for Ischemic Stroke

Neuroscience, Journal Year: 2024, Volume and Issue: 550, P. 69 - 78

Published: May 17, 2024

Despite recent advances in acute stroke management, most patients experiencing a will suffer from residual brain damage and functional impairment. Addressing those deficits would require neurorestoration, i.e., rebuilding tissue to repair the structural caused by stroke. However, there are major pathobiological, anatomical technological hurdles making neurorestorative approaches remarkably challenging, true neurorestoration after larger ischemic lesions could not yet be achieved. On other hand, has been steady advancement our understanding of limits regeneration adult mammalian as well fundamental organization growth during embryo- ontogenesis. This paralleled development novel animal models study stroke, biomaterials that can used support stem cell technologies. review gives detailed explanation so far preventing achievement It also describe concepts advancements biomaterial science, organoid culturing, modeling may enable investigation post-stroke translationally relevant setups. Finally, achievements experimental studies have potential starting point research activities eventually bring within reach.

Language: Английский

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Cell Heterogeneity Uncovered by Single-Cell RNA Sequencing Offers Potential Therapeutic Targets for Ischemic Stroke

Aging and Disease, Journal Year: 2022, Volume and Issue: 13(5), P. 1436 - 1436

Published: Jan. 1, 2022

Ischemic stroke is a detrimental neurological disease characterized by an irreversible infarct core surrounded ischemic penumbra, salvageable region of brain tissue. Unique roles distinct cell subpopulations within the neurovascular unit and peripheral immune cells during remain elusive due to heterogeneity in brain. Single-cell RNA sequencing (scRNA-seq) allows for unbiased determination cellular at high-resolution identification markers, thereby unveiling principal clusters cell-type-specific gene expression patterns as well cell-specific subclusters their functions different pathways underlying stroke. In this review, we have summarized changes differentiation trajectories types highlighted specific genes that are impacted This review expected inspire new research provide directions investigating potential pathological mechanisms novel treatment strategies level single cell.

Language: Английский

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Association of Plasma Biomarkers of Alzheimer Disease and Neurodegeneration With Longitudinal Intra-Network Functional Brain Connectivity

Neurology, Journal Year: 2025, Volume and Issue: 104(4)

Published: Jan. 31, 2025

Alzheimer disease (AD) is defined by cortical β-amyloid (Aβ), tau, and neurodegeneration, which contribute to cognitive decline, in part, altering large-scale functional brain networks. While Aβ tau have been associated with changes connectivity, it unknown whether plasma biomarkers relate such changes. In a healthy community sample of cognitively unimpaired adults free from major CNS the Baltimore Longitudinal Study Aging, we examined AD pathology (Aβ42/40, phosphorylated [pTau-181]), astrogliosis (glial fibrillary acidic protein [GFAP]), neuronal injury (neurofilament light chain [NfL]) were longitudinal connectivity related cognition. Plasma measured using Quanterix SIMOA assays. Intranetwork (3T resting-state fMRI) 7 networks was derived predefined parcellation mask for each participant visit. Cognitive performance assessed concurrently fMRI scan. Covariate-adjusted linear mixed-effect models used determine (1) (2) magnitude biomarker-connectivity relationships differed amyloid status, (3) co-occurred Our primary findings (n = 486; age 65.5 ± 16.2 years; 54% female; mean follow-up time 4.3 1.7 years) showed that higher baseline GFAP faster declines somatomotor (β -0.04, p 0.01, 95% CI -0.06 -0.01), limbic -0.03, 0.02, -0.005), frontoparietal -0.07 -0.01) network connectivity. Amyloid status moderated several associations. For instance, NfL visual but only among amyloid-positive participants. Among 421 participants ≥2 visits (age 71.7 11.4 55% 3.9 1.6 years), concurrent cognition; however, these results did not survive multiple comparison correction. participants, amyloidosis, astrogliosis, are particularly Major limitations include lack inclusion sensitive pTau-217 pTau-231 isoforms comparative PET biomarkers.

Language: Английский

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NAT10 inhibition alleviates astrocyte autophagy by impeding ac4C acetylation of Timp1 mRNA in ischemic stroke

Acta Pharmaceutica Sinica B, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

Language: Английский

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