Reactive gliosis in traumatic brain injury: a comprehensive review

Frontiers in Cellular Neuroscience, Journal Year: 2024, Volume and Issue: 18

Published: Feb. 28, 2024

Traumatic brain injury (TBI) is one of the most common pathological conditions impacting central nervous system (CNS). A neurological deficit associated with TBI results from a complex pathogenetic mechanisms including glutamate excitotoxicity, inflammation, demyelination, programmed cell death, or development edema. The critical components contributing to CNS response, damage control, and regeneration after are glial cells–in reaction tissue damage, their activation, hypertrophy, proliferation occur, followed by formation scar. scar creates barrier in damaged helps protect acute phase post-injury. However, this process prevents complete recovery late/chronic producing permanent scarring, which significantly impacts function. Various types participate formation, but mostly attributed reactive astrocytes microglia, play important roles several pathologies. Novel technologies whole-genome transcriptomic epigenomic analyses, unbiased proteomics, show that both microglia represent groups heterogenic subpopulations different genomic functional characteristics, responsible for role neurodegeneration, neuroprotection regeneration. Depending on representation distinct glia subpopulations, as well regenerative processes delayed neurodegeneration may thus differ nearby remote areas structures. This review summarizes process, where resultant effect severity-, region- time-dependent determined model distance explored area lesion site. Here, we also discuss findings concerning intercellular signaling, long-term possibilities novel therapeutical approaches. We believe comprehensive study an emphasis cells, involved post-injury processes, be helpful further research decisive factor when choosing model.

Language: Английский

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Glial Perturbation in Metal Neurotoxicity: Implications for Brain Disorders

Neuroglia, Journal Year: 2025, Volume and Issue: 6(1), P. 4 - 4

Published: Jan. 6, 2025

Overexposure of humans to heavy metals and essential poses a significant risk for the development neurological neurodevelopmental disorders. The mechanisms through which these exert their effects include generation reactive oxygen species, mitochondrial dysfunction, activation inflammatory pathways, disruption cellular signaling. function glial cells in brain maintenance homeostasis cannot be overlooked. are particularly susceptible metal-induced neurotoxicity. Accumulation promotes microglial activation, triggering responses that can coincide with other neurotoxicity, inducing alteration synaptic transmission, cognitive deficit, neuronal damage. In this review, we highlighted role dysfunction some selected neurodegenerative diseases We further dive into how exposure such as nickel, manganese, methyl mercury, cadmium, iron, arsenic, lead affect functions microglia, astrocytes, oligodendrocytes they on relation Potential therapeutic interventions use new improved chelating agents antioxidant therapies might approach alleviating perturbations.

Language: Английский

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Vitamin E Analog Trolox Attenuates MPTP-Induced Parkinson’s Disease in Mice, Mitigating Oxidative Stress, Neuroinflammation, and Motor Impairment

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(12), P. 9942 - 9942

Published: June 9, 2023

Trolox is a potent antioxidant and water-soluble analog of vitamin E. It has been used in scientific studies to examine oxidative stress its impact on biological systems. shown have neuroprotective effect against ischemia IL-1β-mediated neurodegeneration. In this study, we investigated the potential protective mechanisms 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease mouse model. Western blotting, immunofluorescence staining, ROS/LPO assays were performed investigate role trolox neuroinflammation, mediated by MPTP (PD) model (wild-type mice (C57BL/6N), eight weeks old, average body weight 25-30 g). Our study showed that increased expression α-synuclein, decreased tyrosine hydroxylase (TH) dopamine transporter (DAT) levels striatum substantia nigra pars compacta (SNpc), impaired motor function. However, treatment significantly reversed these PD-like pathologies. Furthermore, reduced increasing nuclear factor erythroid-2-related 2 (Nrf2) heme oxygenase-1 (HO-1). Lastly, inhibited activated astrocytes (GFAP) microglia (Iba-1), also reducing phosphorylated factor-κB, (p-NF-κB) tumor necrosis factor-alpha (TNF-α) PD brain. Overall, our demonstrated may exert neuroprotection dopaminergic neurons MPTP-induced stress, dysfunction,

Language: Английский

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Proteins and Transcriptional Dysregulation of the Brain Extracellular Matrix in Parkinson’s Disease: A Systematic Review

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(8), P. 7435 - 7435

Published: April 18, 2023

The extracellular matrix (ECM) of the brain is a dynamic structure made up vast network bioactive macromolecules that modulate cellular events. Structural, organizational, and functional changes in these due to genetic variation or environmental stressors are thought affect functions may result disease. However, most mechanistic studies date usually focus on aspects diseases pay less attention relevance processes governing nature disease pathogenesis. Thus, ECM's diversified biological roles, increasing interest its involvement disease, lack sufficient compiled evidence regarding relationship with Parkinson's (PD) pathology, we aimed compile existing boost current knowledge area provide refined guidance for future research. Here, this review, gathered postmortem tissue induced pluripotent stem cell (iPSC)-related from PubMed Google Scholar identify, summarize describe common macromolecular alterations expression ECM components (PD). A literature search was conducted until 10 February 2023. overall hits database manual proteomic transcriptome were 1243 1041 articles, respectively. Following full-text articles 24 transcriptomic found be eligible inclusion. According studies, proteins such as collagens, fibronectin, annexins, tenascins recognized differentially expressed Transcriptomic displayed dysregulated pathways including ECM-receptor interaction, focal adhesion, adhesion molecules limited number relevant accessed our search, indicating much work remains carried out better understand roles neurodegeneration believe review will elicit focused primary thus support ongoing efforts discovery development diagnostic biomarkers well therapeutic agents

Language: Английский

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Research progress in the molecular mechanism of ferroptosis in Parkinson's disease and regulation by natural plant products

Ageing Research Reviews, Journal Year: 2023, Volume and Issue: 91, P. 102063 - 102063

Published: Sept. 9, 2023

Language: Английский

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The spatial landscape of glial pathology and T-cell response in Parkinson’s disease substantia nigra

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 9, 2024

Abstract Parkinson’s Disease (PD) is a progressive neurodegenerative disease that leads to debilitating movement disorders and often dementia. Recent evidence, including identification of specific peripheral T-cell receptor sequences, indicates the adaptive immune response associated with pathogenesis. However, properties T-cells in brain regions where neurons degenerate are not well characterized. We have analyzed identities interactions PD post-mortem tissue using single nucleus RNA sequencing, spatial transcriptomics sequencing. found substantia nigra donors exhibit CD8+ resident memory phenotype, increased clonal expansion, altered relationships astrocytes, myeloid cells, endothelial cells. also describe regional differences astrocytic responses neurodegeneration. Our findings nominate potential molecular cellular candidates allow deeper understanding pathophysiology neurodegeneration PD. Together, our work represents major transcriptional resource for fields

Language: Английский

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Cortistatin as a Novel Multimodal Therapy for the Treatment of Parkinson’s Disease

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(2), P. 694 - 694

Published: Jan. 5, 2024

Parkinson’s disease (PD) is a complex disorder characterized by the impairment of dopaminergic nigrostriatal system. PD has duplicated its global burden in last few years, becoming leading neurological disability worldwide. Therefore, there an urgent need to develop innovative approaches that target multifactorial underlying causes potentially prevent or limit progression. Accumulating evidence suggests neuroinflammatory responses may play pivotal role neurodegenerative processes occur during development PD. Cortistatin neuropeptide shown potent anti-inflammatory and immunoregulatory effects preclinical models autoimmune disorders. The goal this study was explore therapeutic potential cortistatin well-established mouse model induced acute exposure neurotoxin 1-methil-4-phenyl1-1,2,3,6-tetrahydropyridine (MPTP). We observed treatment with mitigated MPTP-induced loss neurons substantia nigra their connections striatum. Consequently, administration improved locomotor activity animals intoxicated MPTP. In addition, diminished presence activation glial cells affected brain regions MPTP-treated mice, reduced production immune mediators, promoted expression neurotrophic factors vitro PD, also demonstrated reduction cell death were exposed neurotoxin. Taken together, these findings suggest could emerge as promising new agent combines neuroprotective properties regulate progression at multiple levels.

Language: Английский

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Is Glial Dysfunction the Key Pathogenesis of LRRK2-Linked Parkinson’s Disease?

Biomolecules, Journal Year: 2023, Volume and Issue: 13(1), P. 178 - 178

Published: Jan. 15, 2023

Leucine rich-repeat kinase 2 (LRRK2) is the most well-known etiologic gene for familial Parkinson’s disease (PD). Its product a large with multiple functional domains that phosphorylates subset of Rab small GTPases. However, studies autopsy cases LRRK2 mutations indicate varied pathology, and molecular functions its relationship to PD pathogenesis are largely unknown. Recently, non-autonomous neurodegeneration associated glial cell dysfunction has attracted attention as possible mechanism dopaminergic neurodegeneration. Molecular in astrocytes microglia have also suggested involved regulation lysosomal other organelle dynamics inflammation. In this review, we describe proposed cells discuss involvement pathomechanisms PD.

Language: Английский

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SC-VAR: a computational tool for interpreting polygenic disease risks using single-cell epigenomic data.

Briefings in Bioinformatics, Journal Year: 2025, Volume and Issue: 26(2)

Published: March 4, 2025

One major challenge of interpreting variants from genome-wide association studies (GWAS) complex traits or diseases is how to efficiently annotate noncoding variants. These influence gene expression by disrupting cis-regulatory elements (CREs), whose spatial and cell-type specificity are not adequately captured conventional tools like multi-marker analysis genomic annotation. Current methods either rely on linear proximity genes quantitative trait locus (QTL) data yet fail integrate single-cell epigenomic information for a comprehensive We present SC-VAR, novel computational tool designed enhance the interpretation disease-associated risks GWAS using data. SC-VAR leverages predict functional outcomes including risk genes, pathways, cell types both coding demonstrate that outperforms state-of-the-art predicting more validated disease-related pathways multiple diseases. Additionally, identifies susceptible disease, along with their specific CREs target linked risk. By capturing broad range disease across human tissues at distinct developmental stages, could our understanding mechanisms in different life stages.

Language: Английский

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The Role of Oligodendrocytes in Neurodegenerative Diseases: Unwrapping the Layers

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(10), P. 4623 - 4623

Published: May 12, 2025

Neurodegenerative diseases (NDs), including Alzheimer’s disease, Parkinson’s amyotrophic lateral sclerosis/motor neuron and multiple sclerosis, are characterized by progressive loss of neuronal structure function, leading to severe cognitive, motor, behavioral impairments. They pose a significant growing challenge due their rising prevalence impact on global health systems. The societal emotional toll patients, caregivers, healthcare infrastructures is considerable. While progress has been made in elucidating the pathological hallmarks these disorders, underlying cellular molecular mechanisms remain incompletely understood. Increasing evidence implicates oligodendrocytes progenitors—oligodendrocyte progenitor cells (OPCs)—in pathogenesis several NDs, beyond traditionally recognized role demyelinating conditions such as MS. Oligodendrocytes essential for axonal myelination, metabolic support, neural circuit modulation central nervous system. Disruptions oligodendrocyte function myelin integrity—manifesting demyelination, hypomyelination, or dysmyelination—have associated with disease progression various neurodegenerative contexts. This review consolidates recent findings OPCs explores concept plasticity, discusses therapeutic strategies targeting dysfunction. By highlighting emerging research biology, this aims provide short overview its relevance potential advances.

Language: Английский

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