Translational Neurodegeneration, Journal Year: 2024, Volume and Issue: 13(1)
Published: Sept. 7, 2024
Language: Английский
Nature Neuroscience, Journal Year: 2024, Volume and Issue: 27(5), P. 901 - 912
Published: March 21, 2024
Language: Английский
Citations
6
bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown
Published: May 26, 2024
ABSTRACT The capacity to regenerate myelin in the central nervous system (CNS) diminishes with age. This decline is particularly evident multiple sclerosis (MS), which has been suggested exhibit features of accelerated biological aging. Whether cellular senescence, a hallmark aging, contributes remyelination impairment remains unknown. Here, we show that senescent cells (SCs) accumulate within demyelinated lesions after injury, and their elimination enhances young mice but not aged mice. In mice, observed upregulation senescence-associated transcripts primarily microglia demyelination, followed by reduction during remyelination. However, factors persisted lesions, correlating inefficient We found SC enhanced was ineffective Proteomic analysis secretory phenotype (SASP) revealed elevated levels CCL11/Eotaxin-1 inhibit efficient oligodendrocyte maturation. These results suggest therapeutic targeting SASP components, such as CCL11, may improve aging MS.
Language: Английский
Citations
6
Biomolecules, Journal Year: 2022, Volume and Issue: 12(4), P. 538 - 538
Published: April 2, 2022
Over the past decade, multiple sclerosis (MS), a chronic neuroinflammatory disease with severe personal and social consequences, has undergone steady increase in incidence prevalence rates worldwide. Despite ongoing research development of several novel therapies, MS pathology remains incompletely understood, prospect for curative treatment continues to be unpromising near future. A sustained effort, however, should contribute deeper understanding underlying mechanisms, which will undoubtedly yield improved results drug development. In recent years, blood-brain barrier (BBB) increasingly become focus many studies as it appears involved both onset progression. More specifically, neurovascular unit damage is believed critical process CNS immune cell penetration, subsequently favors CNS-specific response, leading classical pathological clinical hallmarks MS. The aim current narrative review merge relevant evidence on role BBB comprehensive succinct manner. Firstly, physiological structure functions component more complex are presented. Subsequently, authors specific alteration encountered different stages MS, focusing modifications cells neuroinflammation penetration cells. Finally, currently accepted theories neurodegeneration summarized.
Language: Английский
Citations
27
International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(14), P. 7584 - 7584
Published: July 8, 2022
The etiology of multiple sclerosis (MS), a demyelinating disease affecting the central nervous system (CNS), remains obscure. Although apoptosis oligodendrocytes and neurons has been observed in MS lesions, contribution this cell death process to pathogenesis controversial. It is usually considered that MS-associated demyelination axonal degeneration result from neuroinflammation an autoimmune targeting myelin proteins. However, experimental data indicate oligodendrocyte and/or neuronal may indeed precede development inflammation autoimmunity. These findings raise question as whether neural key event initiating driving pathological cascade, leading clinical functional deficits MS. Similarly, regarding damage, feature roles inflammation-independent autonomous processes need be further explored. While loss not necessarily mutually exclusive, particular attention should given role loss. If proven, could viewed primarily neurodegenerative accompanied by secondary neuroinflammatory process.
Language: Английский
Citations
25
International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(20), P. 12387 - 12387
Published: Oct. 16, 2022
Vitronectin (VTN), a multifunctional glycoprotein with various physiological functions, exists in plasma and the extracellular matrix. It is known to be involved cell attachment, spreading migration through binding integrin receptor, mainly via RGD sequence. VTN also widely used maintenance expansion of pluripotent stem cells, but its effects go beyond that. Recent evidence shows more functions nervous system as it participates neural differentiation, neuronutrition neurogenesis, well regulating axon size, supporting guiding neurite extension. Furthermore, was proved play key role protecting brain can reduce permeability blood–brain barrier by interacting receptors vascular endothelial cells. Moreover, suggests that associated neurodegenerative diseases, such Alzheimer’s disease, function has not been fully understood. This review summarizes neurons describes diseases.
Language: Английский
Citations
23
Neuroscience Bulletin, Journal Year: 2022, Volume and Issue: 39(3), P. 541 - 552
Published: Nov. 12, 2022
Abstract Astrocytes (ASTs) and oligodendroglial lineage cells (OLGs) are major macroglial in the central nervous system. ASTs communicate with each other through connexin (Cx) Cx-based network structures, both of which allow for quick transport nutrients signals. Moreover, interact OLGs (Cx)-mediated networks to modulate various physiological processes brain. In this article, following a brief description infrastructural basis glial exocrine factors by may crosstalk, we focus on recapitulating how interactions between these two types myelination, AST-OLG involved protecting integrity blood-brain barrier (BBB) regulating synaptogenesis neural activity. Recent studies further suggest that associated myelin-related diseases, such as multiple sclerosis. A better understanding regulatory mechanisms underlying inspire development novel therapeutic strategies related brain diseases.
Language: Английский
Citations
20
Biomedicines, Journal Year: 2023, Volume and Issue: 11(3), P. 750 - 750
Published: March 1, 2023
BET proteins function as histone code readers of acetylated lysins that determine the positive regulation in transcription genes involved cell cycle progression, differentiation, inflammation, and many other pathways. In recent years, thanks to development inhibitors, interest this protein family has risen for its relevance brain function. For example, experimental evidence shown modulation affects neuronal activity expression learning memory. addition, inhibition strongly suppresses molecular pathways related neuroinflammation. These observations suggest may play a critical role onset during diverse neurodegenerative neuropsychiatric disorders, such Alzheimer’s disease, fragile X syndrome, Rett syndrome. review article, we summarize most regarding involvement physiology pathology, well their pharmacological potential targets therapeutic purposes.
Language: Английский
Citations
13
Immunity Inflammation and Disease, Journal Year: 2023, Volume and Issue: 11(1)
Published: Jan. 1, 2023
Abstract Introduction Among the most frequent demyelinating autoimmune disorders of central nervous system (CNS) is multiple sclerosis. Experimental encephalomyelitis (EAE) used as an animal model Berberine alkaloid found in some medicinal plants with anti‐inflammatory effects. Methods C57BL/6 female mice were and divided into three groups: (1) The control group received PBS, (2) low‐dose treatment 10 mg/kg berberine, (3) high‐dose 30 berberine. Myelin Oligodendrocyte Glycoprotein complete Freund's adjuvant subcutaneously administered to induce EAE. Mice given intraperitoneal injections pertussis toxin on day immunization 2 days later. Histological studies showed low lymphocyte infiltration demyelination CNS treated groups. Results clinical scores berberine (T1: ± 0.13) (T2: 1.5 0.14) significantly ( p < .001) lower than (CTRL: 4.5 0.13). Treatment groups decreased pro‐inflammatory cytokines (IFN‐γ, TNF‐α, interleukin [IL]‐17) well increased cytokine expression (IL‐4, IL‐10, IL‐27, IL‐33, IL‐35, TGF‐β) .01) when compared CTRL group. reduced Th1 Th17 transcription factors Th2 Treg contrast Conclusion appears have a protective effect disease development alleviating status EAE, which be due cell expansion function cells addition berberine's properties.
Language: Английский
Citations
11
Translational Stroke Research, Journal Year: 2024, Volume and Issue: unknown
Published: Aug. 21, 2024
Specific inflammatory pathways are important in the development of delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage. Understanding specific inflammation may be critical for finding new treatments. Evidence is accumulating that innate cells and proteins play a more role than adaptive system. In this work, we review evidence from clinical preclinical data regarding which immune system DCI with particular emphasis on bone-marrow-derived monocytes neutrophils brain parenchymal microglia. addition, will complement proteins, non-cellular part system, DCI.
Language: Английский
Citations
4
Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)
Published: March 7, 2025
The capacity to regenerate myelin in the central nervous system diminishes with age. This decline is particularly evident multiple sclerosis (MS), a chronic demyelinating disease. Whether cellular senescence, hallmark of aging, contributes remyelination impairment remains unknown. Here, we show that senescent cells accumulate within demyelinated lesions after injury, and treatments senolytics enhances young middle-aged mice but not aged mice. In mice, observe upregulation senescence-associated transcripts, primarily microglia macrophages, demyelination, followed by reduction during remyelination. However, factors persist lesions, correlating inefficient Proteomic analysis secretory phenotype (SASP) reveals elevated levels CCL11/Eotaxin-1 which found inhibit oligodendrocyte maturation. These results suggest therapeutic targeting SASP components, such as CCL11, may improve aging MS. impact on authors treatment following demyelination young, these effects are mediated including CCL11.
Language: Английский
Citations
0