Neuroinflammation Induces Myelin Damage by Inhibiting Gapdh of Oligodendrocytes in the Hippocampus DOI Creative Commons

Zhongjia Li,

Huiqun Fu,

Fangyan Liu

и другие.

Research Square (Research Square), Год журнала: 2024, Номер unknown

Опубликована: Июнь 5, 2024

Abstract Background Myelin damage has been detected in central nervous system disease accompanied by neuroinflammation and cognitive dysfunction. However, the mechanism of myelin associated with aged brain not clarified. Methods We explored induced hippocampus rats through both vivo vitro approaches from perspective energy synthesis oligodendrocytes. developed a model single intraperitoneal injection LPS determined dysfunction hippocampus. Single-cell RNA sequencing was employed to exam gene expression changes related oligodendrocytes identified Gapdh as significantly downregulated gene. In vitro, OLN-93 cells were differentiate into mature treated TNF-α. The effect Gapdh on TNF-α-induced suppression MBP reduction oligodendrocytes, mitochondrial damage, assessed Gapdhoverexpression. Results rats, spatial learning memory impairments triggered LPS, alongside neuroinflammatory responses, as evidenced elevated levels TNF-α IL-1β Additionally, there protein disorganization within structure, which notably thinner LPS-treated group. proportion oligodendrocyte clusters myelination remyelination decreased, level decreased each cluster apoptosis reduced GAPDH expression. glycolysis oxidative phosphorylation ability lactate concentration ATP content. Mitochondrial stress also detected. Overexpression improved Conclusions Neuroinflammation impairs functions phosphorylation, mitochondria inhibiting Lack support decreases basic levels, subsequently resulting deterioration, may lead

Язык: Английский

Glial Cells as Key Regulators in Neuroinflammatory Mechanisms Associated with Multiple Sclerosis DOI Open Access

Styliani Theophanous,

Irene Sargiannidou, Kleopas A. Kleopa

и другие.

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(17), С. 9588 - 9588

Опубликована: Сен. 4, 2024

Even though several highly effective treatments have been developed for multiple sclerosis (MS), the underlying pathological mechanisms and drivers of disease not fully elucidated. In recent years, there has a growing interest in studying neuroinflammation context glial cell involvement as is increasing evidence their central role progression. Although communication proper function underlies brain homeostasis maintenance, effects an MS remain complex controversial. this review, we aim to provide overview contribution cells, oligodendrocytes, astrocytes, microglia pathology during both activation orchestration inflammatory mechanisms, well synergistic repair restoration function. Additionally, discuss how understanding may new therapeutic targets either limit progression or facilitate repair.

Язык: Английский

Процитировано

8
The interplay of inflammation and remyelination: rethinking MS treatment with a focus on oligodendrocyte progenitor cells DOI Creative Commons
Omri Zveik, Ariel Rechtman, Tal Ganz

и другие.

Molecular Neurodegeneration, Год журнала: 2024, Номер 19(1)

Опубликована: Июль 12, 2024

Multiple sclerosis (MS) therapeutic goals have traditionally been dichotomized into two distinct avenues: immune-modulatory-centric interventions and pro-regenerative strategies. Oligodendrocyte progenitor cells (OPCs) were regarded for many years solely in concern to their potential generate oligodendrocytes myelin the central nervous system (CNS). However, accumulating data elucidate multifaceted roles of OPCs, including immunomodulatory functions, positioning them as cardinal constituents CNS's immune landscape.

Язык: Английский

Процитировано

7
The Rise of Pluripotent Stem Cell-Derived Glia Models of Neuroinflammation DOI Creative Commons
Srishti Kala, Andrew G. Strutz, Moriah E. Katt

и другие.

Neurology International, Год журнала: 2025, Номер 17(1), С. 6 - 6

Опубликована: Янв. 13, 2025

Neuroinflammation is a blanket term that describes the body’s complex inflammatory response in central nervous system (CNS). It encompasses phenotype shift to proinflammatory state, release of cytokines, recruitment peripheral immune cells, and wide variety other processes. has been implicated nearly every major CNS disease ranging from Alzheimer’s brain cancer. Understanding modeling neuroinflammation critical for identification novel therapeutic targets treatment diseases. Unfortunately, translation findings non-human models left much be desired. This review systematically discusses role human pluripotent stem cell (hPSC)-derived glia supporting cells within CNS, including astrocytes, microglia, oligodendrocyte precursor pericytes, endothelial describe state field hope future discoveries. hPSC-derived offer an expanded potential study pathobiology immunomodulatory cascades impact progression. While progress made development models, there explore application these understand CNS.

Язык: Английский

Процитировано

0
Unlocking the Potential: immune functions of oligodendrocyte precursor cells DOI Creative Commons

Amr Haroon,

Harsha Seerapu,

Li‐Pao Fang

и другие.

Frontiers in Immunology, Год журнала: 2024, Номер 15

Опубликована: Июль 9, 2024

Oligodendrocyte precursor cells (OPCs) have long been regarded as progenitors of oligodendrocytes, yet recent advances illuminated their multifaceted nature including emerging immune functions. This review seeks to shed light on the functions exhibited by OPCs, spanning from phagocytosis modulation and direct engagement with across various pathological scenarios. Comprehensive understanding OPCs alongside other roles will pave way for targeted therapies in neurological disorders.

Язык: Английский

Процитировано

3
Mechanism of tumor-associated macrophages with PD-1 monoclonal antibodies affecting vascular generation in cervical cancer via the PD-1/IRE1α/SHP2/HIF1α signaling pathway DOI Creative Commons
Xiaohui Hao, Weiwei Zhao, Xianyu Zhang

и другие.

Aging, Год журнала: 2024, Номер 16(17), С. 12335 - 12345

Опубликована: Авг. 28, 2024

Objective: To investigate the effect of PD-1 monoclonal antibodies in tumor-associated macrophages on angiogenesis cervical cancer and its mechanism action. Methods: The progression was assessed using nude mouse xenograft model HE staining; impact cell migration evaluated wound healing assay Transwell assay; vascular formation cells examined an expression related proteins tested Western blotting. Results: can regulate thus inhibit while promoting SHP2. Additionally, Sindilizumab inhibited tissue-type fibrinogen activator K HIF1α through PD-1/IRE1α/SHP2 signaling pathway, which neovascularization cells. Conclusions: This study discovered that generation inside by affecting PD-1/IRE1α/SHP2/HIF1α providing a new therapeutic target for treatment cancer.

Язык: Английский

Процитировано

0
Pro-Inflammatory Molecules Implicated in Multiple Sclerosis Divert the Development of Human Oligodendrocyte Lineage Cells DOI Creative Commons
Gabriela J. Blaszczyk, Abdulshakour Mohammadnia, Valerio E. C. Piscopo

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Дек. 17, 2024

Abstract Background and Objectives Oligodendrocytes (OL) their myelin-forming processes are targeted lost during the disease course of Multiple Sclerosis (MS), by infiltrating leukocytes effector cytokines. Myelin repair is considered to be dependent on recruitment differentiation oligodendrocyte precursor cells (OPCs). The basis failure re-myelination MS remains defined. aim this study determine impact pro-inflammatory molecules tumor necrosis factor ⍰ (TNF⍰) interferon gamma (IFN γ ) human OPCs. Methods We generated OPCs from induced pluripotent stem with a reporter gene under OL-specific transcription SOX10. treated in vitro TNF⍰ or IFN evaluated effects terms cell viability, expression OL-lineage markers, co- astrocyte markers. To relate our findings molecular properties as found brain we re-analyzed publicly available single nuclear RNAseq datasets. Results Our analysis indicated that both decreased proportion differentiating into OL-lineage; consistent previous reports. now observe effect linked aberrant OPC differentiation. A subset O4+, reporter-positive expressed astrocytic marker Aquaporin-4 (AQP4). On transcriptomic level, acquire an astrocyte-like signature alongside conserved reactive phenotype. Analysis single- datasets revealed expressing signature. Discussion In context MS, these results imply present but inhibited along OL-lineage, acquiring stem-cell like phenotype, reducing capacity contribute towards repair. These help define potential for impaired myelin provide prospective route regenerative treatment.

Язык: Английский

Процитировано

0
Neuroinflammation Induces Myelin Damage by Inhibiting Gapdh of Oligodendrocytes in the Hippocampus DOI Creative Commons

Zhongjia Li,

Huiqun Fu,

Fangyan Liu

и другие.

Research Square (Research Square), Год журнала: 2024, Номер unknown

Опубликована: Июнь 5, 2024

Abstract Background Myelin damage has been detected in central nervous system disease accompanied by neuroinflammation and cognitive dysfunction. However, the mechanism of myelin associated with aged brain not clarified. Methods We explored induced hippocampus rats through both vivo vitro approaches from perspective energy synthesis oligodendrocytes. developed a model single intraperitoneal injection LPS determined dysfunction hippocampus. Single-cell RNA sequencing was employed to exam gene expression changes related oligodendrocytes identified Gapdh as significantly downregulated gene. In vitro, OLN-93 cells were differentiate into mature treated TNF-α. The effect Gapdh on TNF-α-induced suppression MBP reduction oligodendrocytes, mitochondrial damage, assessed Gapdhoverexpression. Results rats, spatial learning memory impairments triggered LPS, alongside neuroinflammatory responses, as evidenced elevated levels TNF-α IL-1β Additionally, there protein disorganization within structure, which notably thinner LPS-treated group. proportion oligodendrocyte clusters myelination remyelination decreased, level decreased each cluster apoptosis reduced GAPDH expression. glycolysis oxidative phosphorylation ability lactate concentration ATP content. Mitochondrial stress also detected. Overexpression improved Conclusions Neuroinflammation impairs functions phosphorylation, mitochondria inhibiting Lack support decreases basic levels, subsequently resulting deterioration, may lead

Язык: Английский

Процитировано

0