scholarly journals Insulin signaling mediates neurodegeneration in glioma

2021 ◽  
Vol 4 (3) ◽  
pp. e202000693
Author(s):  
Patricia Jarabo ◽  
Carmen de Pablo ◽  
Héctor Herranz ◽  
Francisco Antonio Martín ◽  
Sergio Casas-Tintó
Keyword(s):  
Brain Tumors ◽  
Neuronal Degeneration ◽  
Cell Communication ◽  
Premature Death ◽  
Insulin Pathway ◽  
Communication Signals ◽  
Synapse Loss ◽  
Surrounding Healthy Tissue ◽  
Insulin Activity ◽  
Mitochondrial Disruption

Cell to cell communication facilitates tissue development and physiology. Under pathological conditions, brain tumors disrupt glia-neuron communication signals that in consequence, promote tumor expansion at the expense of surrounding healthy tissue. The glioblastoma is one of the most aggressive and frequent primary brain tumors. This type of glioma expands and infiltrates into the brain, causing neuronal degeneration and neurological decay, among other symptoms. Here, we describe in a Drosophila model how glioblastoma cells produce ImpL2, an antagonist of the insulin pathway, which targets neighboring neurons and causes mitochondrial disruption as well as synapse loss, both early symptoms of neurodegeneration. Furthermore, glioblastoma progression requires insulin pathway attenuation in neurons. Restoration of neuronal insulin activity is sufficient to rescue synapse loss and to delay the premature death caused by glioma. Therefore, signals from glioblastoma to neuron emerge as a potential field of study to prevent neurodegeneration and to develop anti-tumoral strategies.

scholarly journals Insulin signaling mediates neurodegeneration in glioma

2020 ◽  
Author(s):  
Patricia Jarabo ◽  
Carmen de Pablo ◽  
Héctor Herranz ◽  
Francisco Antonio Martín ◽  
Sergio Casas-Tintó
Keyword(s):  
Insulin Signaling ◽  
Neuronal Degeneration ◽  
Tumour Progression ◽  
Cell Communication ◽  
Premature Death ◽  
Insulin Pathway ◽  
Communication Signals ◽  
Synapse Loss ◽  
Neurodegenerative Process ◽  
Mitochondrial Disruption

AbstractCell to cell communication facilitates tissue development and physiology. Under pathological conditions, brain tumors disrupt glia-neuron communication signals that in consequence, promote tumor expansion at the expense of surrounding healthy tissue. The glioblastoma is the most aggressive and frequent brain tumor. This type of glioma expands and infiltrates into the brain, causing neuronal degeneration and neurological decay, among other symptoms. Here we describe how the glioblastoma produce ImpL2, an antagonist of the insulin pathway, which is regulated by the microRNA miR-8. ImpL2 targets neighboring neurons and causes mitochondrial disruption as well as synapse loss, both early symptoms of neurodegeneration. Furthermore, glioblastoma progression requires insulin pathway attenuation in neurons. Restoration of neuronal insulin activity is sufficient to rescue the synapse loss and to delay the premature death caused by glioma. Therefore, signals from GB to neuron emerge as a potential field of study to prevent neurodegeneration and to develop anti-tumoral strategies.Significance StatementGlioblastoma (GB) is the most aggressive type of brain tumour and currently there is no cure or effective treatment. Patients course with neurological decay and previous data in animal models indicate that GB cause a neurodegenerative process. We describe here a molecule named ImpL2 that is produced by GB cells and impact on neighbouring neurons. ImpL2 is an antagonist of the insulin pathway and signaling reduction in neurons causes mitochondrial defects and synapse loss. These mechanisms underlying GB-induced neurodegeneration plays a central role in the premature death caused by this tumour. Restoration of insulin signaling in neurons prevents tumour progression and rescues the lethality caused by GB in Drosophila models.

The cis -2-dodecenoic acid (BDSF) quorum sensing system in Burkholderia cenocepacia

2022 ◽  
Author(s):  
Mingfang Wang ◽  
Xia Li ◽  
Shihao Song ◽  
Chaoyu Cui ◽  
Lian-Hui Zhang ◽  
...  
Keyword(s):  
Quorum Sensing ◽  
Bacterial Infections ◽  
Xanthomonas Campestris ◽  
Cell Communication ◽  
Burkholderia Cenocepacia ◽  
Bacterial Cells ◽  
Communication Signals ◽  
Signal Perception ◽  
Sensing System ◽  
Diffusible Signal Factor

It has been demonstrated that quorum sensing (QS) is widely employed by bacterial cells to coordinately regulate various group behaviors. Diffusible signal factor (DSF)-type signals have emerged as a growing family of conserved cell-cell communication signals. In addition to the DSF signal initially identified in Xanthomonas campestris pv. campestris, B urkholderia d iffusible s ignal f actor (BDSF, cis -2-dodecenoic acid) has been recognized as a conserved DSF-type signal with specific characteristics in both signal perception and transduction from DSF signals. Here, we review the history and current progress of the research of this type of signal, especially focusing on its biosynthesis, signaling pathways, and biological functions. We also discuss and explore the huge potential of targeting this kind of QS system as a new therapeutic strategy to control bacterial infections and diseases.

scholarly journals Interspecies Communication in Holobionts by Non-Coding RNA Exchange

2020 ◽  
Vol 21 (7) ◽  
pp. 2333
Author(s):  
Ana Lúcia Leitão ◽  
Marina C. Costa ◽  
André F. Gabriel ◽  
Francisco J. Enguita
Keyword(s):  
Target Cell ◽  
Current Knowledge ◽  
Cell Communication ◽  
Special Focus ◽  
Interspecies Communication ◽  
Communication Signals ◽  
Non Coding Rna ◽  
Molecular Machinery ◽  
Non Coding Rnas

Complex organisms are associations of different cells that coexist and collaborate creating a living consortium, the holobiont. The relationships between the holobiont members are essential for proper homeostasis of the organisms, and they are founded on the establishment of complex inter-connections between all the cells. Non-coding RNAs are regulatory molecules that can also act as communication signals between cells, being involved in either homeostasis or dysbiosis of the holobionts. Eukaryotic and prokaryotic cells can transmit signals via non-coding RNAs while using specific extracellular conveyors that travel to the target cell and can be translated into a regulatory response by dedicated molecular machinery. Within holobionts, non-coding RNA regulatory signaling is involved in symbiotic and pathogenic relationships among the cells. This review analyzes current knowledge regarding the role of non-coding RNAs in cell-to-cell communication, with a special focus on the signaling between cells in multi-organism consortia.

scholarly journals iTALK: an R Package to Characterize and Illustrate Intercellular Communication

2019 ◽  
Author(s):  
Yuanxin Wang ◽  
Ruiping Wang ◽  
Shaojun Zhang ◽  
Shumei Song ◽  
Changying Jiang ◽  
...  
Keyword(s):  
Intercellular Communication ◽  
Cell Communication ◽  
R Package ◽  
Therapy Resistance ◽  
Computational Approach ◽  
Sequencing Data ◽  
Communication Signals ◽  
Cellular Processes ◽  
Wide Range ◽  
Single Cell Rna Sequencing

ABSTRACTCrosstalk between tumor cells and other cells within the tumor microenvironment (TME) plays a crucial role in tumor progression, metastases, and therapy resistance. We present iTALK, a computational approach to characterize and illustrate intercellular communication signals in the multicellular tumor ecosystem using single-cell RNA sequencing data. iTALK can in principle be used to dissect the complexity, diversity, and dynamics of cell-cell communication from a wide range of cellular processes.

Defining the expression, production, and signaling roles of specialized metabolites during Bacillus subtilis differentiation

2021 ◽  
Author(s):  
Alexi A. Schoenborn ◽  
Sarah M. Yannarell ◽  
E. Diane Wallace ◽  
Haley Clapper ◽  
Ilon C. Weinstein ◽  
...  
Keyword(s):  
Bacillus Subtilis ◽  
Biofilm Formation ◽  
Cell Communication ◽  
Signaling Molecules ◽  
Interspecies Interactions ◽  
Communication Signals ◽  
Specialized Metabolites ◽  
Growing Body ◽  
Antagonistic Potential ◽  
Cell Cell

Bacterial specialized (or secondary) metabolites are structurally diverse molecules that mediate intra- and interspecies interactions by altering growth and cellular physiology and differentiation. Bacillus subtilis , a Gram-positive model bacterium commonly used to study biofilm formation and sporulation, has the capacity to produce over ten specialized metabolites. Some of these B. subtilis specialized metabolites have been investigated for their role in facilitating cellular differentiation, only rarely has the behavior of multiple metabolites been simultaneously investigated. In this study, we explored the interconnectivity of differentiation (biofilm and sporulation) and specialized metabolites in B. subtilis . Specifically, we interrogated how development influences specialized metabolites and vice versa. Using the sporulation-inducing medium DSM, we found that the majority of the specialized metabolites examined are expressed and produced during biofilm formation and sporulation. Additionally, we found that six of these metabolites (surfactin, ComX, bacillibactin, bacilysin, subtilosin A, and plipastatin) are necessary signaling molecules for proper progression of B. subtilis differentiation. This study further supports the growing body of work demonstrating that specialized metabolites have essential physiological functions as cell-cell communication signals in bacteria. Importance/Significance Bacterially produced specialized metabolites are frequently studied for their potential use as antibiotics and antifungals. However, a growing body of work has suggested that the antagonistic potential of specialized metabolites is not their only function. Here, using Bacillus subtilis as our model bacterium, we demonstrated that developmental processes such as biofilm formation and sporulation are tightly linked with specialized metabolite gene expression and production. Additionally, under our differentiation-inducing conditions, six out of the nine specialized metabolites investigated behave as intraspecific signals that impact B. subtilis physiology and influence biofilm formation and sporulation. Our work supports the viewpoint that specialized metabolites have a clear role as cell-cell signaling molecules within differentiated populations of bacteria.

scholarly journals Structural and Functional Characterization of Diffusible Signal Factor Family Quorum-Sensing Signals Produced by Members of the Burkholderia cepacia Complex

2010 ◽  
Vol 76 (14) ◽  
pp. 4675-4683 ◽  
Author(s):  
Yinyue Deng ◽  
Ji'en Wu ◽  
Leo Eberl ◽  
Lian-Hui Zhang
Keyword(s):  
Quorum Sensing ◽  
Burkholderia Cepacia ◽  
High Performance ◽  
Xanthomonas Campestris ◽  
Functional Characterization ◽  
Cell Communication ◽  
Burkholderia Cenocepacia ◽  
Burkholderia Cepacia Complex ◽  
Communication Signals ◽  
Diffusible Signal Factor

ABSTRACT Previous work has shown that Burkholderia cenocepacia produces the diffusible signal factor (DSF) family signal cis-2-dodecenoic acid (C12:Δ2, also known as BDSF), which is involved in the regulation of virulence. In this study, we determined whether C12:Δ2 production is conserved in other members of the Burkholderia cepacia complex (Bcc) by using a combination of high-performance liquid chromatography, mass spectrometry, and bioassays. Our results show that five Bcc species are capable of producing C12:Δ2 as a sole DSF family signal, while four species produce not only C12:Δ2 but also a new DSF family signal, which was identified as cis,cis-11-methyldodeca-2,5-dienoic acid (11-Me-C12:Δ2,5). In addition, we demonstrate that the quorum-sensing signal cis-11-methyl-2-dodecenoic acid (11-Me-C12:Δ2), which was originally identified in Xanthomonas campestris supernatants, is produced by Burkholderia multivorans. It is shown that, similar to 11-Me-C12:Δ2 and C12:Δ2, the newly identified molecule 11-Me-C12:Δ2,5 is a potent signal in the regulation of biofilm formation, the production of virulence factors, and the morphological transition of Candida albicans. These data provide evidence that DSF family molecules are highly conserved bacterial cell-cell communication signals that play key roles in the ecology of the organisms that produce them.

scholarly journals Intermediary role of macrophages in the passage of suppressor signals between T-cell subsets.

1978 ◽  
Vol 148 (2) ◽  
pp. 424-434 ◽  
Author(s):  
W Ptak ◽  
M Zembala ◽  
R K Gershon
Keyword(s):  
T Cells ◽  
T Cell ◽  
Active Form ◽  
Cell Communication ◽  
Contact Hypersensitivity ◽  
T Cell Subsets ◽  
Specific Factor ◽  
Communication Signals ◽  
Cell Surface Structures ◽  
Intermediary Role

We have examined the ability of macrophages (Mphi) to transmit T-cell derived suppressor signals to other T cells. The suppressor signal studied is an antigen-specific factor which suppresses the ability of adoptively transferred, sensitized lymphocytes to express contact hypersensitivity in normal recipients. We have found that this factor binds to peritoneal exudate Mphi via cell surface structures which can be blocked with heat-aggregated gamma globulin. Dead (HK) Mphi bind the factor but fail to present it in a functional way to assay (immune) T cells, whereas live (L) Mphi perform both functions. Further, L Mphi can retrieve the factor in an active form from the surfaces of HK Mphi. Based on these and other findings (1-5), we discuss the possibility that Mphi may play as important a role in presenting T-cell communication signals to the cells of the immune system as they do in presenting antigen.

scholarly journals Targeted complement inhibition at synapses prevents microglial synaptic engulfment and synapse loss in demyelinating disease

2019 ◽  
Author(s):  
Sebastian Werneburg ◽  
Jonathan Jung ◽  
Rejani B. Kunjamma ◽  
Seung-Kwon Ha ◽  
Nicholas J. Luciano ◽  
...  
Keyword(s):  
Neurodegenerative Diseases ◽  
Immune Cell ◽  
Demyelinating Disease ◽  
Neuronal Degeneration ◽  
Striking Similarity ◽  
Gene Therapy Approach ◽  
Synapse Loss ◽  
Complement Component C3 ◽  
Axon Loss ◽  
The Central Nervous System

SummaryMultiple sclerosis (MS) is a demyelinating, autoimmune disease of the central nervous system. While work has focused on axon loss in MS, far less is known about synaptic changes. Here, in striking similarity to other neurodegenerative diseases, we identify in postmortem human MS tissue and in nonhuman primate and mouse MS models profound synapse loss and microglial synaptic engulfment. These events can occur independently of local demyelination, neuronal degeneration, and peripheral immune cell infiltration, but coincide with gliosis and increased localization of complement component C3, but not C1q, at synapses. Finally, we use AAV9 to overexpress the complement inhibitor Crry at activated C3-bound synapses in mice and demonstrate robust protection of synapses and visual function. These results mechanistically dissect synapse loss as an early pathology in MS. We further provide a novel gene therapy approach to prevent synapse loss by microglia, which may be broadly applicable to other neurodegenerative diseases.

scholarly journals Microglia Mediate Early Corticostriatal Synapse Loss and Cognitive Dysfunction in Huntington’s Disease Through Complement-Dependent Mechanisms

2021 ◽  
Author(s):  
D.K. Wilton ◽  
K. Mastro ◽  
M.D. Heller ◽  
F.W. Gergits ◽  
C R. Willing ◽  
...  
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Molecular Mechanisms ◽  
Neuronal Degeneration ◽  
Early Stage ◽  
Innate Immune ◽  
Mutant Huntingtin ◽  
Genetic Ablation ◽  
Complement Proteins ◽  
Synapse Loss

AbstractHuntington’s disease (HD) is a devastating monogenic neurodegenerative disease characterized by early, selective pathology in the basal ganglia despite the ubiquitous expression of mutant huntingtin. The molecular mechanisms underlying this region-specific neuronal degeneration and how these relate to the development of early cognitive phenotypes are poorly understood. Here, we show that there is selective loss of synaptic connections between the cortex and striatum in postmortem tissue from HD patients that is associated with the increased activation and localization of complement proteins, innate immune molecules, to markers of these synaptic elements. We also find that levels of these secreted innate immune molecules are elevated in the CSF of premanifest HD patients and correlate with established measures of disease burden.In preclinical genetic models of HD we show that complement proteins mediate the selective elimination of corticostriatal synapses at an early stage in disease pathogenesis marking them for removal by microglia, the brain’s resident macrophage population. This process requires mutant huntingtin to be expressed in both cortical and striatal neurons and inhibition of this complement-dependent elimination mechanism through administration of a therapeutically relevant C1q function blocking antibody or genetic ablation of a complement receptor on microglia, prevented synapse loss, increased excitatory input to the striatum and rescued the early development of visual discrimination learning and cognitive flexibility deficits in these models. Together, our findings implicate microglia and the complement cascade in the selective, early degeneration of corticostriatal synapses and the development of cognitive deficits in presymptomatic HD, and also provide new preclinical data to support complement as a therapeutic target for early intervention.

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