S100A4 in the Physiology and Pathology of the Central and Peripheral Nervous System

D’Ambrosi, Nadia; Milani, M; Apolloni, Savina

doi:10.3390/cells10040798

Cited by 20 publications

(10 citation statements)

References 82 publications

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“…There was no significant cell death was observed regardless the treatments applied ( Figure S3 A). It has been showed that inflammation have an effect on neuron differentiation 39 , 40 . Next, we sought to determine the neuronal differentiation in these cells treated with brain metabolites from GaELNs or PBS treated HFD mice.…”

Section: Resultsmentioning

confidence: 99%

Garlic exosome-like nanoparticles reverse high-fat diet induced obesity via the gut/brain axis

Sundaram¹,

Mu²,

Kumar³

et al. 2022

Theranostics

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Background: Obesity is becoming a global epidemic and reversing the pathological processes underlying obesity and metabolic co-morbidities is challenging. Obesity induced chronic inflammation including brain inflammation is a hallmark of obesity via the gut-brain axis. The objective of this study was to develop garlic exosome-like nanoparticles (GaELNs) that inhibit systemic as well as brain inflammatory activity and reverse a HFD induced obesity in mice. Methods: GELNs were isolated and administrated orally into HFD fed mice. GaELNs were fluorescent labeled for monitoring their in vivo trafficking route after oral administration and quantified the number particles in several tissues. The brain inflammation was determined by measuring inflammatory cytokines by ELISA and real-time PCR. Mitochondrial membrane permeability of microglial cells was determined using JC-10 fluorescence dye. The in vivo apoptotic cell death was quantified by TUNEL assay. The brain metabolites were identified and quantified by LC-MS analysis. Memory function of the mice was determined by several memory functional analysis. The effect of GaELNs on glucose and insulin response of the mice was determined by glucose and insulin tolerance tests. c-Myc localization and interaction with BASP1 and calmodulin was determined by confocal microscopy. Results: Our results show that GaELNs is preferentially taken up microglial cells and inhibits the brain inflammation in HFD mice. GaELN phosphatidic acid (PA) (36:4) is required for the uptake of GaELNs via interaction with microglial BASP1. Formation of the GaELNs/BASP1 complex is required for inhibition of c-Myc mediated expression of STING. GaELN PA binds to BASP1, leading to inhibition of c-Myc expression and activity through competitively binding to CaM with c-Myc transcription factor. Inhibition of STING activity leads to reducing the expression of an array of inflammatory cytokines including IFN-γ and TNF-α. IFN-γ induces the expression of IDO1, which in turn the metabolites generated as IDO1 dependent manner activate the AHR pathway that contributes to developing obesity. The metabolites derived from the GaELNs treated microglial cells promote neuronal differentiation and inhibit mitochondrial mediated neuronal cell death. GaELNs treated HFD mice showed improved memory function and increased glucose tolerance and insulin sensitivity in these mice. Conclusion : Collectively, these results demonstrate how nanoparticles from a healthy diet can inhibit unhealthy high-fat diet induced brain inflammation and reveal a link between brain microglia/diet to brain inflammatory disease outcomes via diet-derived exosome-like nanoparticles.

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Section: Resultsmentioning

confidence: 99%

Garlic exosome-like nanoparticles reverse high-fat diet induced obesity via the gut/brain axis

Sundaram¹,

Mu²,

Kumar³

et al. 2022

Theranostics

View full text Add to dashboard Cite

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“…For example, TMEM16F inhibitor niclosamide and its analogs nitazoxanide, hexachlorophene and dichlorophen, present with intriguing anthelmintic, anticancer, and anti-ALS properties, indicating similar pathogenesis ( Peng et al., 2021 ). Indeed, as these agents target S100A4, a protein involved in schizophrenia and inhibited by the phenothiazine class of antipsychotic drugs, a common pathogenetic mechanism is being highlighted ( Malashkevich et al., 2010 ; D’Ambrosi et al., 2021 ). In addition, since S100A4 has also been implicated in tumorigenesis, it may be the common denominator between viral illness, cancer, and neuropsychiatric disorders ( Fei et al., 2017 ).…”

Section: Treatment Strategies For Pathological Cell-cell Fusionmentioning

confidence: 99%

Virus-Induced Membrane Fusion in Neurodegenerative Disorders

Osorio

Sfera

Anton

et al. 2022

Front. Cell. Infect. Microbiol.

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A growing body of epidemiological and research data has associated neurotropic viruses with accelerated brain aging and increased risk of neurodegenerative disorders. Many viruses replicate optimally in senescent cells, as they offer a hospitable microenvironment with persistently elevated cytosolic calcium, abundant intracellular iron, and low interferon type I. As cell-cell fusion is a major driver of cellular senescence, many viruses have developed the ability to promote this phenotype by forming syncytia. Cell-cell fusion is associated with immunosuppression mediated by phosphatidylserine externalization that enable viruses to evade host defenses. In hosts, virus-induced immune dysfunction and premature cellular senescence may predispose to neurodegenerative disorders. This concept is supported by novel studies that found postinfectious cognitive dysfunction in several viral illnesses, including human immunodeficiency virus-1, herpes simplex virus-1, and SARS-CoV-2. Virus-induced pathological syncytia may provide a unified framework for conceptualizing neuronal cell cycle reentry, aneuploidy, somatic mosaicism, viral spreading of pathological Tau and elimination of viable synapses and neurons by neurotoxic astrocytes and microglia. In this narrative review, we take a closer look at cell-cell fusion and vesicular merger in the pathogenesis of neurodegenerative disorders. We present a “decentralized” information processing model that conceptualizes neurodegeneration as a systemic illness, triggered by cytoskeletal pathology. We also discuss strategies for reversing cell-cell fusion, including, TMEM16F inhibitors, calcium channel blockers, senolytics, and tubulin stabilizing agents. Finally, going beyond neurodegeneration, we examine the potential benefit of harnessing fusion as a therapeutic strategy in regenerative medicine.

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“…S100A4 controls different cellular pathways, exerting numerous effects on processes that are cell- and tissue-type dependent. In activated fibroblasts, endothelial, dendritic, and mast cells, as well as in macrophages, monocytes, neutrophils, and T-lymphocytes, S100A4 has a significant role in stimulating invasion and migration, cytoskeletal dynamics and in promoting proinflammatory phenotypes [ 14 ]. S100A4 represents a well-known marker that characterizes a complex biological process where endothelial cells assume a mesenchymal phenotype, known as the “endothelial-to mesenchymal transition”, changing morphology and functions, acquiring accentuated motility and contractile properties, typical of fibrotic processes [ 15 ].…”

Section: Discussionmentioning

confidence: 99%

An Integrative Study of Aortic mRNA/miRNA Longitudinal Changes in Long-Term LVAD Support

Dlouhá

Ivák

Netuka

et al. 2021

IJMS

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Studying the long-term impact of continuous-flow left ventricular assist device (CF-LVAD) offers an opportunity for a complex understanding of the pathophysiology of vascular changes in aortic tissue in response to a nonphysiological blood flow pattern. Our study aimed to analyze aortic mRNA/miRNA expression changes in response to long-term LVAD support. Paired aortic samples obtained at the time of LVAD implantation and at the time of heart transplantation were examined for mRNA/miRNA profiling. The number of differentially expressed genes (Pcorr < 0.05) shared between samples before and after LVAD support was 277. The whole miRNome profile revealed 69 differentially expressed miRNAs (Pcorr < 0.05). Gene ontology (GO) analysis identified that LVAD predominantly influenced genes involved in the extracellular matrix and collagen fibril organization. Integrated mRNA/miRNA analysis revealed that potential targets of miRNAs dysregulated in explanted samples are mainly involved in GO biological process terms related to dendritic spine organization, neuron projection organization, and cell junction assembly and organization. We found differentially expressed genes participating in vascular tissue engineering as a consequence of LVAD duration. Changes in aortic miRNA levels demonstrated an effect on molecular processes involved in angiogenesis.

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S100A4 in the Physiology and Pathology of the Central and Peripheral Nervous System

Cited by 20 publications

References 82 publications

Garlic exosome-like nanoparticles reverse high-fat diet induced obesity via the gut/brain axis

Garlic exosome-like nanoparticles reverse high-fat diet induced obesity via the gut/brain axis

Virus-Induced Membrane Fusion in Neurodegenerative Disorders

An Integrative Study of Aortic mRNA/miRNA Longitudinal Changes in Long-Term LVAD Support

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