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  1. Article ; Online: Mediator complex in neurological disease.

    Schiano, Concetta / Luongo, Livio / Maione, Sabatino / Napoli, Claudio

    Life sciences

    2023  Volume 329, Page(s) 121986

    Abstract: Neurological diseases, including traumatic brain injuries, stroke (haemorrhagic and ischemic), and inherent neurodegenerative diseases cause acquired disability in humans, representing a leading cause of death worldwide. The Mediator complex (MED) is a ... ...

    Abstract Neurological diseases, including traumatic brain injuries, stroke (haemorrhagic and ischemic), and inherent neurodegenerative diseases cause acquired disability in humans, representing a leading cause of death worldwide. The Mediator complex (MED) is a large, evolutionarily conserved multiprotein that facilities the interaction between transcription factors and RNA Polymerase II in eukaryotes. Some MED subunits have been found altered in the brain, although their specific functions in neurodegenerative diseases are not fully understood. Mutations in MED subunits were associated with a wide range of genetic diseases for MED12, MED13, MED13L, MED20, MED23, MED25, and CDK8 genes. In addition, MED12 and MED23 were deregulated in the Alzheimer's Disease. Interestingly, most of the genomic mutations have been found in the subunits of the kinase module. To date, there is only one evidence on MED1 involvement in post-stroke cognitive deficits. Although the underlying neurodegenerative disorders may be different, we are confident that the signal cascades of the biological-cognitive mechanisms of brain adaptation, which begin after brain deterioration, may also differ. Here, we analysed relevant studies in English published up to June 2023. They were identified through a search of electronic databases including PubMed, Medline, EMBASE and Scopus, including search terms such as "Mediator complex", "neurological disease", "brains". Thematic content analysis was conducted to collect and summarize all studies demonstrating MED alteration to understand the role of this central transcriptional regulatory complex in the brain. Improved and deeper knowledge of the regulatory mechanisms in neurological diseases can increase the ability of physicians to predict onset and progression, thereby improving diagnostic care and providing appropriate treatment decisions.
    MeSH term(s) Humans ; Cyclin-Dependent Kinase 8/genetics ; Cyclin-Dependent Kinase 8/metabolism ; Transcription Factors/metabolism ; Mutation ; Mediator Complex/genetics
    Chemical Substances Cyclin-Dependent Kinase 8 (EC 2.7.11.22) ; Transcription Factors ; MED25 protein, human ; Mediator Complex
    Language English
    Publishing date 2023-07-28
    Publishing country Netherlands
    Document type Journal Article ; Review
    ZDB-ID 3378-9
    ISSN 1879-0631 ; 0024-3205
    ISSN (online) 1879-0631
    ISSN 0024-3205
    DOI 10.1016/j.lfs.2023.121986
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Mediator complex in neurological disease

    Schiano, Concetta / Luongo, Livio / Maione, Sabatino / Napoli, Claudio

    Life Sciences. 2023 Sept., v. 329 p.121986-

    2023  

    Abstract: Neurological diseases, including traumatic brain injuries, stroke (haemorrhagic and ischemic), and inherent neurodegenerative diseases cause acquired disability in humans, representing a leading cause of death worldwide. The Mediator complex (MED) is a ... ...

    Abstract Neurological diseases, including traumatic brain injuries, stroke (haemorrhagic and ischemic), and inherent neurodegenerative diseases cause acquired disability in humans, representing a leading cause of death worldwide. The Mediator complex (MED) is a large, evolutionarily conserved multiprotein that facilities the interaction between transcription factors and RNA Polymerase II in eukaryotes. Some MED subunits have been found altered in the brain, although their specific functions in neurodegenerative diseases are not fully understood. Mutations in MED subunits were associated with a wide range of genetic diseases for MED12, MED13, MED13L, MED20, MED23, MED25, and CDK8 genes. In addition, MED12 and MED23 were deregulated in the Alzheimer's Disease. Interestingly, most of the genomic mutations have been found in the subunits of the kinase module. To date, there is only one evidence on MED1 involvement in post-stroke cognitive deficits. Although the underlying neurodegenerative disorders may be different, we are confident that the signal cascades of the biological-cognitive mechanisms of brain adaptation, which begin after brain deterioration, may also differ. Here, we analysed relevant studies in English published up to June 2023. They were identified through a search of electronic databases including PubMed, Medline, EMBASE and Scopus, including search terms such as “Mediator complex”, “neurological disease”, “brains”. Thematic content analysis was conducted to collect and summarize all studies demonstrating MED alteration to understand the role of this central transcriptional regulatory complex in the brain. Improved and deeper knowledge of the regulatory mechanisms in neurological diseases can increase the ability of physicians to predict onset and progression, thereby improving diagnostic care and providing appropriate treatment decisions.
    Keywords Alzheimer disease ; DNA-directed RNA polymerase ; brain ; cognition ; death ; eukaryotic cells ; genomics ; stroke ; transcription (genetics) ; Mediator complex ; Personalized medicine ; Neurological diseases
    Language English
    Dates of publication 2023-09
    Publishing place Elsevier Inc.
    Document type Article ; Online
    ZDB-ID 3378-9
    ISSN 1879-0631 ; 0024-3205
    ISSN (online) 1879-0631
    ISSN 0024-3205
    DOI 10.1016/j.lfs.2023.121986
    Database NAL-Catalogue (AGRICOLA)

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  3. Article: Adenosine Metabotropic Receptors in Chronic Pain Management.

    Luongo, Livio / Guida, Francesca / Maione, Sabatino / Jacobson, Kenneth A / Salvemini, Daniela

    Frontiers in pharmacology

    2021  Volume 12, Page(s) 651038

    Language English
    Publishing date 2021-04-16
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2587355-6
    ISSN 1663-9812
    ISSN 1663-9812
    DOI 10.3389/fphar.2021.651038
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Synergistic effects of Boswellia serrata and Acmella oleracea extract combination for treating neuropathic pain in a preclinical model of spared nerve injury.

    Boccella, Serena / Mattia, Consalvo / Perrone, Michela / Morace, Andrea Maria / Karabacak, Elif / Guida, Francesca / Maione, Sabatino / Luongo, Livio

    Phytotherapy research : PTR

    2023  Volume 38, Issue 4, Page(s) 1731–1734

    MeSH term(s) Humans ; Boswellia ; Neuralgia/drug therapy ; Plant Extracts/pharmacology ; Plant Extracts/therapeutic use ; Immunologic Factors
    Chemical Substances Plant Extracts ; Immunologic Factors
    Language English
    Publishing date 2023-09-04
    Publishing country England
    Document type Letter
    ZDB-ID 639136-9
    ISSN 1099-1573 ; 0951-418X
    ISSN (online) 1099-1573
    ISSN 0951-418X
    DOI 10.1002/ptr.8001
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Targeting metabotropic adenosine receptors for neuropathic pain: Focus on A2A.

    Luongo, Livio / Salvemini, Daniela

    Brain, behavior, and immunity

    2018  Volume 69, Page(s) 60–61

    MeSH term(s) Adenosine A2 Receptor Agonists ; Humans ; Injections, Spinal ; Neuralgia ; Receptors, Purinergic P1
    Chemical Substances Adenosine A2 Receptor Agonists ; Receptors, Purinergic P1
    Language English
    Publishing date 2018-03-01
    Publishing country Netherlands
    Document type Journal Article ; Comment
    ZDB-ID 639219-2
    ISSN 1090-2139 ; 0889-1591
    ISSN (online) 1090-2139
    ISSN 0889-1591
    DOI 10.1016/j.bbi.2018.02.014
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article: Editorial: Glial Cells, Maladaptive Plasticity, and Neurodegeneration: Mechanisms, Targeted Therapies, and Future Directions.

    Korai, Sohaib Ali / Sepe, Giovanna / Luongo, Livio / Cragnolini, Andrea Beatriz / Cirillo, Giovanni

    Frontiers in cellular neuroscience

    2021  Volume 15, Page(s) 682524

    Language English
    Publishing date 2021-04-30
    Publishing country Switzerland
    Document type Editorial
    ZDB-ID 2452963-1
    ISSN 1662-5102
    ISSN 1662-5102
    DOI 10.3389/fncel.2021.682524
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Buprenorphine: Far Beyond the "Ceiling".

    Infantino, Rosmara / Mattia, Consalvo / Locarini, Pamela / Pastore, Antonio Luigi / Maione, Sabatino / Luongo, Livio

    Biomolecules

    2021  Volume 11, Issue 6

    Abstract: Chronic pain, including neuropathic pain, represents an untreated disease with important repercussions on the quality of life and huge costs on the national health system. It is well known that opioids are the most powerful analgesic drugs, but they ... ...

    Abstract Chronic pain, including neuropathic pain, represents an untreated disease with important repercussions on the quality of life and huge costs on the national health system. It is well known that opioids are the most powerful analgesic drugs, but they represent the second or third line in neuropathic pain, that remain difficult to manage. Moreover, these drugs show several side effects that limit their use. In addition, opioids possess addictive properties that are associated with misuse and drug abuse. Among available opioids compounds, buprenorphine has been suggested advantageous for a series of clinical reasons, including the effectiveness in neuropathic pain. Some properties are partly explained by its unique pharmacological characteristics. However, questions on the dynamic profile remain to be answered. Pharmacokinetics optimization strategies, and additional potentialities, are still to be explored. In this paper, we attempt to conceptualize the potential undiscovered dynamic profile of buprenorphine.
    MeSH term(s) Analgesics/pharmacokinetics ; Analgesics/therapeutic use ; Buprenorphine/pharmacokinetics ; Buprenorphine/therapeutic use ; Chronic Pain/drug therapy ; Chronic Pain/metabolism ; Humans ; Neuralgia/drug therapy ; Neuralgia/metabolism ; Quality of Life
    Chemical Substances Analgesics ; Buprenorphine (40D3SCR4GZ)
    Language English
    Publishing date 2021-05-31
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2701262-1
    ISSN 2218-273X ; 2218-273X
    ISSN (online) 2218-273X
    ISSN 2218-273X
    DOI 10.3390/biom11060816
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: New Targets for Treating Chronic Pain and Inflammation.

    Guida, Francesca / Luongo, Livio / Di Cesare Mannelli, Lorenzo

    Current medicinal chemistry

    2018  Volume 25, Issue 32, Page(s) 3828–3829

    MeSH term(s) Analgesics/therapeutic use ; Animals ; Anti-Inflammatory Agents/therapeutic use ; Chronic Pain/drug therapy ; Humans ; Inflammation/drug therapy ; Signal Transduction/drug effects
    Chemical Substances Analgesics ; Anti-Inflammatory Agents
    Language English
    Publishing date 2018-10-24
    Publishing country United Arab Emirates
    Document type Editorial
    ZDB-ID 1319315-6
    ISSN 1875-533X ; 0929-8673
    ISSN (online) 1875-533X
    ISSN 0929-8673
    DOI 10.2174/092986732532181016111537
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article: A "double-edged" role for type-5 metabotropic glutamate receptors in pain disclosed by light-sensitive drugs.

    Notartomaso, Serena / Antenucci, Nico / Mazzitelli, Mariacristina / Rovira, Xavier / Boccella, Serena / Ricciardi, Flavia / Liberatore, Francesca / Gomez-Santacana, Xavier / Imbriglio, Tiziana / Cannella, Milena / Zussy, Charleine / Luongo, Livio / Maione, Sabatino / Goudet, Cyril / Battaglia, Giuseppe / Llebaria, Amadeu / Nicoletti, Ferdinando / Neugebauer, Volker

    bioRxiv : the preprint server for biology

    2024  

    Abstract: Knowing the site of drug action is important to optimize effectiveness and address any side effects. We used light-sensitive drugs to identify the brain region-specific role of mGlu5 metabotropic glutamate receptors in the control of pain. Optical ... ...

    Abstract Knowing the site of drug action is important to optimize effectiveness and address any side effects. We used light-sensitive drugs to identify the brain region-specific role of mGlu5 metabotropic glutamate receptors in the control of pain. Optical activation of systemic JF-NP-26, a caged, normally inactive, negative allosteric modulator (NAM) of mGlu5 receptors, in cingulate, prelimbic and infralimbic cortices and thalamus inhibited neuropathic pain hypersensitivity. Systemic treatment of alloswitch-1, an intrinsically active mGlu5 receptor NAM, caused analgesia, and the effect was reversed by light-induced drug inactivation in in the prelimbic and infralimbic cortices, and thalamus. This demonstrates that mGlu5 receptor blockade in the medial prefrontal cortex and thalamus is both sufficient and necessary for the analgesic activity of mGlu5 receptor antagonists. Surprisingly, when light was delivered in the basolateral amygdala, local activation of systemic JF-NP-26 reduced pain thresholds, whereas inactivation of alloswitch-1 enhanced analgesia. Electrophysiological analysis showed that alloswitch-1 increased excitatory synaptic responses in prelimbic pyramidal neurons evoked by stimulation of BLA input, and decreased feedforward inhibition of amygdala output neurons by BLA. Both effects were reversed by optical silencing and reinstated by optical reactivation of alloswitch-1. These findings demonstrate for the first time that the action of mGlu5 receptors in the pain neuraxis is not homogenous, and suggest that blockade of mGlu5 receptors in the BLA may limit the overall analgesic activity of mGlu5 receptor antagonists. This could explain the suboptimal effect of mGlu5 NAMs on pain in human studies and validate photopharmacology as an important tool to determine ideal target sites for systemic drugs.
    Language English
    Publishing date 2024-01-03
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2024.01.02.573945
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Spinal neuronal activity and neuroinflammatory component in a mouse model of CFA-induced vestibulodynia.

    Boccella, Serena / Perrone, Michela / Fusco, Antimo / Bonsale, Roozbe / Infantino, Rosmara / Nuzzo, Silvia / Pecoraro, Giovanni / Ricciardi, Federica / Maria Morace, Andrea / Petrillo, Gianluca / Leone, Ilaria / Franzese, Monica / de Novellis, Vito / Guida, Francesca / Salvatore, Marco / Maione, Sabatino / Luongo, Livio

    Brain, behavior, and immunity

    2024  Volume 119, Page(s) 408–415

    Abstract: Vestibulodynia is a complex pain disorder characterized by chronic discomfort in the vulvar region, often accompanied by tactile allodynia and spontaneous pain. In patients a depressive behaviour is also observed. In this study, we have used a model of ... ...

    Abstract Vestibulodynia is a complex pain disorder characterized by chronic discomfort in the vulvar region, often accompanied by tactile allodynia and spontaneous pain. In patients a depressive behaviour is also observed. In this study, we have used a model of vestibulodynia induced by complete Freund's adjuvant (CFA) focusing our investigation on the spinal cord neurons and microglia. We investigated tactile allodynia, spontaneous pain, and depressive-like behavior as key behavioral markers of vestibulodynia. In addition, we conducted in vivo electrophysiological recordings to provide, for the first time to our knowledge, the characterization of the spinal sacral neuronal activity in the L6-S1 dorsal horn of the spinal cord. Furthermore, we examined microglia activation in the L6-S1 dorsal horn using immunofluorescence, unveiling hypertrophic phenotypes indicative of neuroinflammation in the spinal cord. This represents a novel insight into the role of microglia in vestibulodynia pathology. To address the therapeutic aspect, we employed pharmacological interventions using GABApentin, amitriptyline, and PeaPol. Remarkably, all three drugs, also used in clinic, showed efficacy in alleviating tactile allodynia and depressive-like behavior. Concurrently, we also observed a normalization of the altered neuronal firing and a reduction of microglia hypertrophic phenotypes. In conclusion, our study provides a comprehensive understanding of the CFA-induced model of vestibulodynia, encompassing behavioral, neurophysiological and neuroinflammatory aspects. These data pave the way to investigate spinal cord first pain plasticity in vestibulodynia.
    Language English
    Publishing date 2024-04-16
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 639219-2
    ISSN 1090-2139 ; 0889-1591
    ISSN (online) 1090-2139
    ISSN 0889-1591
    DOI 10.1016/j.bbi.2024.04.012
    Database MEDical Literature Analysis and Retrieval System OnLINE

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