LIVIVO - The Search Portal for Life Sciences

zur deutschen Oberfläche wechseln
Advanced search

Search results

Result 1 - 7 of total 7

Search options

  1. Article ; Online: Src family kinases (SFKs): critical regulators of microglial homeostatic functions and neurodegeneration in Parkinson's and Alzheimer's diseases

    Portugal, Camila C. / Almeida, Tiago O. / Socodato, Renato / Relvas, João B.

    The FEBS Journal. 2022 Dec., v. 289, no. 24 p.7760-7775

    2022  

    Abstract: c‐Src was the first protein kinase to be described as capable of phosphorylating tyrosine residues. Subsequent identification of other tyrosine‐phosphorylating protein kinases with a similar structure to c‐Src gave rise to the concept of Src family ... ...

    Abstract c‐Src was the first protein kinase to be described as capable of phosphorylating tyrosine residues. Subsequent identification of other tyrosine‐phosphorylating protein kinases with a similar structure to c‐Src gave rise to the concept of Src family kinases (SFKs). Microglia are the resident innate immune cell population of the CNS. Under physiological conditions, microglia actively participate in brain tissue homeostasis, continuously patrolling the neuronal parenchyma and exerting neuroprotective actions. Activation of pathogen‐associated molecular pattern (PAMP) and damage‐associated molecular pattern (DAMP) receptors induces microglial proliferation, migration toward pathological foci, phagocytosis, and changes in gene expression, concurrent with the secretion of cytokines, chemokines, and growth factors. A significant body of literature shows that SFK stimulation positively associates with microglial activation and neuropathological conditions, including Alzheimer's and Parkinson's diseases. Here, we review essential microglial homeostatic functions regulated by SFKs, including phagocytosis, environmental sensing, and secretion of inflammatory mediators. In addition, we discuss the potential of SFK modulation for microglial homeostasis in Parkinson's and Alzheimer's diseases.
    Keywords Alzheimer disease ; brain ; chemokines ; homeostasis ; neurodegenerative diseases ; neuroglia ; parenchyma (animal tissue) ; pathogen-associated molecular patterns ; phagocytosis ; protein kinases ; secretion ; tyrosine
    Language English
    Dates of publication 2022-12
    Size p. 7760-7775.
    Publishing place John Wiley & Sons, Ltd
    Document type Article ; Online
    Note REVIEW
    ZDB-ID 2173655-8
    ISSN 1742-4658 ; 1742-464X
    ISSN (online) 1742-4658
    ISSN 1742-464X
    DOI 10.1111/febs.16197
    Database NAL-Catalogue (AGRICOLA)

    Full text online

    More links

    Kategorien

    In stock of ZB MED Bonn / Germany

    Z 2006/704: Show issues

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

  2. Article ; Online: Src family kinases (SFKs): critical regulators of microglial homeostatic functions and neurodegeneration in Parkinson's and Alzheimer's diseases.

    Portugal, Camila C / Almeida, Tiago O / Socodato, Renato / Relvas, João B

    The FEBS journal

    2021  

    Abstract: c-Src was the first protein kinase to be described as capable of phosphorylating tyrosine residues. Subsequent identification of other tyrosine-phosphorylating protein kinases with a similar structure to c-Src gave rise to the concept of Src family ... ...

    Abstract c-Src was the first protein kinase to be described as capable of phosphorylating tyrosine residues. Subsequent identification of other tyrosine-phosphorylating protein kinases with a similar structure to c-Src gave rise to the concept of Src family kinases (SFKs). Microglia are the resident innate immune cell population of the CNS. Under physiological conditions, microglia actively participate in brain tissue homeostasis, continuously patrolling the neuronal parenchyma and exerting neuroprotective actions. Activation of pathogen-associated molecular pattern (PAMP) and damage-associated molecular pattern (DAMP) receptors induces microglial proliferation, migration toward pathological foci, phagocytosis, and changes in gene expression, concurrent with the secretion of cytokines, chemokines, and growth factors. A significant body of literature shows that SFK stimulation positively associates with microglial activation and neuropathological conditions, including Alzheimer's and Parkinson's diseases. Here, we review essential microglial homeostatic functions regulated by SFKs, including phagocytosis, environmental sensing, and secretion of inflammatory mediators. In addition, we discuss the potential of SFK modulation for microglial homeostasis in Parkinson's and Alzheimer's diseases.
    Language English
    Publishing date 2021-09-12
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 2173655-8
    ISSN 1742-4658 ; 1742-464X
    ISSN (online) 1742-4658
    ISSN 1742-464X
    DOI 10.1111/febs.16197
    Database MEDical Literature Analysis and Retrieval System OnLINE

    Full text online

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.A 260: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  3. Article ; Online: RhoA balances microglial reactivity and survival during neuroinflammation.

    Socodato, Renato / Rodrigues-Santos, Artur / Tedim-Moreira, Joana / Almeida, Tiago O / Canedo, Teresa / Portugal, Camila C / Relvas, João B

    Cell death & disease

    2023  Volume 14, Issue 10, Page(s) 690

    Abstract: Microglia are the largest myeloid cell population in the brain. During injury, disease, or inflammation, microglia adopt different functional states primarily involved in restoring brain homeostasis. However, sustained or exacerbated microglia ... ...

    Abstract Microglia are the largest myeloid cell population in the brain. During injury, disease, or inflammation, microglia adopt different functional states primarily involved in restoring brain homeostasis. However, sustained or exacerbated microglia inflammatory reactivity can lead to brain damage. Dynamic cytoskeleton reorganization correlates with alterations of microglial reactivity driven by external cues, and proteins controlling cytoskeletal reorganization, such as the Rho GTPase RhoA, are well positioned to refine or adjust the functional state of the microglia during injury, disease, or inflammation. Here, we use multi-biosensor-based live-cell imaging approaches and tissue-specific conditional gene ablation in mice to understand the role of RhoA in microglial response to inflammation. We found that a decrease in RhoA activity is an absolute requirement for microglial metabolic reprogramming and reactivity to inflammation. However, without RhoA, inflammation disrupts Ca
    MeSH term(s) Mice ; Animals ; Microglia/metabolism ; Neuroinflammatory Diseases ; Inflammation/metabolism ; Necrosis/metabolism ; Apoptosis
    Language English
    Publishing date 2023-10-20
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2541626-1
    ISSN 2041-4889 ; 2041-4889
    ISSN (online) 2041-4889
    ISSN 2041-4889
    DOI 10.1038/s41419-023-06217-w
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  4. Article ; Online: Correction: RhoA balances microglial reactivity and survival during neuroinflammation.

    Socodato, Renato / Rodrigues-Santos, Artur / Tedim-Moreira, Joana / Almeida, Tiago O / Canedo, Teresa / Portugal, Camila C / Relvas, João B

    Cell death & disease

    2023  Volume 14, Issue 12, Page(s) 808

    Language English
    Publishing date 2023-12-08
    Publishing country England
    Document type Published Erratum
    ZDB-ID 2541626-1
    ISSN 2041-4889 ; 2041-4889
    ISSN (online) 2041-4889
    ISSN 2041-4889
    DOI 10.1038/s41419-023-06340-8
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  5. Article ; Online: Microglial Rac1 is essential for experience-dependent brain plasticity and cognitive performance.

    Socodato, Renato / Almeida, Tiago O / Portugal, Camila C / Santos, Evelyn C S / Tedim-Moreira, Joana / Galvão-Ferreira, João / Canedo, Teresa / Baptista, Filipa I / Magalhães, Ana / Ambrósio, António F / Brakebusch, Cord / Rubinstein, Boris / Moreira, Irina S / Summavielle, Teresa / Pinto, Inês Mendes / Relvas, João B

    Cell reports

    2023  Volume 42, Issue 12, Page(s) 113447

    Abstract: Microglia, the largest population of brain immune cells, continuously interact with synapses to maintain brain homeostasis. In this study, we use conditional cell-specific gene targeting in mice with multi-omics approaches and demonstrate that the ... ...

    Abstract Microglia, the largest population of brain immune cells, continuously interact with synapses to maintain brain homeostasis. In this study, we use conditional cell-specific gene targeting in mice with multi-omics approaches and demonstrate that the RhoGTPase Rac1 is an essential requirement for microglia to sense and interpret the brain microenvironment. This is crucial for microglia-synapse crosstalk that drives experience-dependent plasticity, a fundamental brain property impaired in several neuropsychiatric disorders. Phosphoproteomics profiling detects a large modulation of RhoGTPase signaling, predominantly of Rac1, in microglia of mice exposed to an environmental enrichment protocol known to induce experience-dependent brain plasticity and cognitive performance. Ablation of microglial Rac1 affects pathways involved in microglia-synapse communication, disrupts experience-dependent synaptic remodeling, and blocks the gains in learning, memory, and sociability induced by environmental enrichment. Our results reveal microglial Rac1 as a central regulator of pathways involved in the microglia-synapse crosstalk required for experience-dependent synaptic plasticity and cognitive performance.
    MeSH term(s) Microglia/metabolism ; Neuronal Plasticity ; Cognition/physiology ; Animals ; Mice ; Neuropeptides/genetics ; Neuropeptides/physiology ; rac1 GTP-Binding Protein/genetics ; rac1 GTP-Binding Protein/physiology ; Male ; Female ; Mice, Mutant Strains ; Synapses/physiology ; Brain/physiology ; Gene Knockdown Techniques
    Chemical Substances Rac1 protein, mouse ; Neuropeptides ; rac1 GTP-Binding Protein (EC 3.6.5.2)
    Language English
    Publishing date 2023-11-18
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2649101-1
    ISSN 2211-1247 ; 2211-1247
    ISSN (online) 2211-1247
    ISSN 2211-1247
    DOI 10.1016/j.celrep.2023.113447
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  6. Article ; Online: Daily alcohol intake triggers aberrant synaptic pruning leading to synapse loss and anxiety-like behavior.

    Socodato, Renato / Henriques, Joana F / Portugal, Camila C / Almeida, Tiago O / Tedim-Moreira, Joana / Alves, Renata L / Canedo, Teresa / Silva, Cátia / Magalhães, Ana / Summavielle, Teresa / Relvas, João B

    Science signaling

    2020  Volume 13, Issue 650

    Abstract: Alcohol abuse adversely affects the lives of millions of people worldwide. Deficits in synaptic transmission and in microglial function are commonly found in human alcohol abusers and in animal models of alcohol intoxication. Here, we found that a ... ...

    Abstract Alcohol abuse adversely affects the lives of millions of people worldwide. Deficits in synaptic transmission and in microglial function are commonly found in human alcohol abusers and in animal models of alcohol intoxication. Here, we found that a protocol simulating chronic binge drinking in male mice resulted in aberrant synaptic pruning and substantial loss of excitatory synapses in the prefrontal cortex, which resulted in increased anxiety-like behavior. Mechanistically, alcohol intake increased the engulfment capacity of microglia in a manner dependent on the kinase Src, the subsequent activation of the transcription factor NF-κB, and the consequent production of the proinflammatory cytokine TNF. Pharmacological blockade of Src activation or of TNF production in microglia, genetic ablation of
    MeSH term(s) Animals ; Anxiety/physiopathology ; Anxiety/psychology ; Behavior, Animal/drug effects ; Behavior, Animal/physiology ; Cells, Cultured ; Central Nervous System Depressants/administration & dosage ; Ethanol/administration & dosage ; Ethanol/blood ; Humans ; Male ; Mice, Inbred C57BL ; Mice, Knockout ; Mice, Transgenic ; Microglia/cytology ; Microglia/drug effects ; Microglia/metabolism ; Neuronal Plasticity/drug effects ; Neuronal Plasticity/physiology ; Synapses/drug effects ; Synapses/physiology ; Synaptic Transmission/drug effects ; Synaptic Transmission/physiology ; Tumor Necrosis Factor-alpha/metabolism
    Chemical Substances Central Nervous System Depressants ; Tumor Necrosis Factor-alpha ; Ethanol (3K9958V90M)
    Language English
    Publishing date 2020-09-22
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2417226-1
    ISSN 1937-9145 ; 1945-0877
    ISSN (online) 1937-9145
    ISSN 1945-0877
    DOI 10.1126/scisignal.aba5754
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  7. Article ; Online: Microglia Dysfunction Caused by the Loss of Rhoa Disrupts Neuronal Physiology and Leads to Neurodegeneration.

    Socodato, Renato / Portugal, Camila C / Canedo, Teresa / Rodrigues, Artur / Almeida, Tiago O / Henriques, Joana F / Vaz, Sandra H / Magalhães, João / Silva, Cátia M / Baptista, Filipa I / Alves, Renata L / Coelho-Santos, Vanessa / Silva, Ana Paula / Paes-de-Carvalho, Roberto / Magalhães, Ana / Brakebusch, Cord / Sebastião, Ana M / Summavielle, Teresa / Ambrósio, António F /
    Relvas, João B

    Cell reports

    2020  Volume 31, Issue 12, Page(s) 107796

    Abstract: Nervous tissue homeostasis requires the regulation of microglia activity. Using conditional gene targeting in mice, we demonstrate that genetic ablation of the small GTPase Rhoa in adult microglia is sufficient to trigger spontaneous microglia activation, ...

    Abstract Nervous tissue homeostasis requires the regulation of microglia activity. Using conditional gene targeting in mice, we demonstrate that genetic ablation of the small GTPase Rhoa in adult microglia is sufficient to trigger spontaneous microglia activation, producing a neurological phenotype (including synapse and neuron loss, impairment of long-term potentiation [LTP], formation of β-amyloid plaques, and memory deficits). Mechanistically, loss of Rhoa in microglia triggers Src activation and Src-mediated tumor necrosis factor (TNF) production, leading to excitotoxic glutamate secretion. Inhibiting Src in microglia Rhoa-deficient mice attenuates microglia dysregulation and the ensuing neurological phenotype. We also find that the Rhoa/Src signaling pathway is disrupted in microglia of the APP/PS1 mouse model of Alzheimer disease and that low doses of Aβ oligomers trigger microglia neurotoxic polarization through the disruption of Rhoa-to-Src signaling. Overall, our results indicate that disturbing Rho GTPase signaling in microglia can directly cause neurodegeneration.
    MeSH term(s) Aging/metabolism ; Aging/pathology ; Amyloid beta-Peptides/metabolism ; Animals ; CSK Tyrosine-Protein Kinase ; Cell Line ; Cell Polarity ; Cell Survival ; Mice, Inbred C57BL ; Microglia/metabolism ; Microglia/pathology ; Nerve Degeneration/pathology ; Neurons/metabolism ; Phenotype ; Synapses/metabolism ; rhoA GTP-Binding Protein/deficiency ; rhoA GTP-Binding Protein/metabolism ; src-Family Kinases/antagonists & inhibitors ; src-Family Kinases/metabolism
    Chemical Substances Amyloid beta-Peptides ; CSK Tyrosine-Protein Kinase (EC 2.7.10.2) ; src-Family Kinases (EC 2.7.10.2) ; RhoA protein, mouse (EC 3.6.5.2) ; rhoA GTP-Binding Protein (EC 3.6.5.2)
    Language English
    Publishing date 2020-06-21
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2649101-1
    ISSN 2211-1247 ; 2211-1247
    ISSN (online) 2211-1247
    ISSN 2211-1247
    DOI 10.1016/j.celrep.2020.107796
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

To top