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  1. Article ; Online: Traditional and Innovative Anti-seizure Medications Targeting Key Physiopathological Mechanisms: Focus on Neurodevelopment and Neurodegeneration.

    Sciaccaluga, Miriam / Ruffolo, Gabriele / Palma, Eleonora / Costa, Cinzia

    Current neuropharmacology

    2023  Volume 21, Issue 8, Page(s) 1736–1754

    Abstract: Despite the wide range of compounds currently available to treat epilepsy, there is still no drug that directly tackles the physiopathological mechanisms underlying its development. Indeed, antiseizure medications attempt to prevent seizures but are ... ...

    Abstract Despite the wide range of compounds currently available to treat epilepsy, there is still no drug that directly tackles the physiopathological mechanisms underlying its development. Indeed, antiseizure medications attempt to prevent seizures but are inefficacious in counteracting or rescuing the physiopathological phenomena that underlie their onset and recurrence, and hence do not cure epilepsy. Classically, the altered excitation/inhibition balance is postulated as the mechanism underlying epileptogenesis and seizure generation. This oversimplification, however, does not account for deficits in homeostatic plasticity resulting from either insufficient or excessive compensatory mechanisms in response to a change in network activity. In this respect, both neurodevelopmental epilepsies and those associated with neurodegeneration may share common underlying mechanisms that still need to be fully elucidated. The understanding of these molecular mechanisms shed light on the identification of new classes of drugs able not only to suppress seizures, but also to present potential antiepileptogenic effects or "disease-modifying" properties.
    MeSH term(s) Animals ; Humans ; Anticonvulsants/pharmacology ; Anticonvulsants/therapeutic use ; Epilepsy/drug therapy ; Epilepsy/prevention & control ; Disease Models, Animal
    Chemical Substances Anticonvulsants
    Language English
    Publishing date 2023-05-04
    Publishing country United Arab Emirates
    Document type Journal Article
    ZDB-ID 2192352-8
    ISSN 1875-6190 ; 1570-159X
    ISSN (online) 1875-6190
    ISSN 1570-159X
    DOI 10.2174/1570159X21666230504160948
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 6150: Show issues Location:
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  2. Article ; Online: Classical and Unexpected Effects of Ultra-Micronized PEA in Neuromuscular Function.

    Cifelli, Pierangelo / Ruffolo, Gabriele / Ceccanti, Marco / Cambieri, Chiara / Libonati, Laura / Palma, Eleonora / Inghilleri, Maurizio

    Biomolecules

    2022  Volume 12, Issue 6

    Abstract: Recently, the endocannabinoid system has attracted growing attention from the scientific community for its involvement in homeostatic and pathological processes as they pertains to human physiology. Among the constituents of the endocannabinoid system, ... ...

    Abstract Recently, the endocannabinoid system has attracted growing attention from the scientific community for its involvement in homeostatic and pathological processes as they pertains to human physiology. Among the constituents of the endocannabinoid system, the molecule palmitoyl ethanolamide has particularly been studied for its ability to reduce several inflammatory processes involving the central nervous system. Here, we reviewed published literature and summarized the main targets of the palmitoyl ethanolamide, along with its unique possible mechanisms for restoring correct functioning of the central nervous system. Moreover, we have highlighted a less-known characteristic of palmitoyl ethanolamide, namely its ability to modulate the function of the neuromuscular junction by binding to acetylcholine receptors in different experimental conditions. Indeed, there are several studies that have highlighted how ultra-micronized palmitoyl ethanolamide is an interesting nutraceutical support for the treatment of pathological neuromuscular conditions, specifically when the normal activity of the acetylcholine receptor is altered. Although further multicentric clinical trials are needed to confirm the efficacy of ultra-micronized palmitoyl ethanolamide in improving symptoms of neuromuscular diseases, all the literature reviewed here strongly supports the ability of this endocannabinoid-like molecule to modulate the acetylcholine receptors thus resulting as a valid support for the treatment of human neuromuscular diseases.
    MeSH term(s) Endocannabinoids/metabolism ; Humans ; Neuromuscular Diseases/drug therapy ; Receptors, Cholinergic
    Chemical Substances Endocannabinoids ; Receptors, Cholinergic
    Language English
    Publishing date 2022-05-29
    Publishing country Switzerland
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 2701262-1
    ISSN 2218-273X ; 2218-273X
    ISSN (online) 2218-273X
    ISSN 2218-273X
    DOI 10.3390/biom12060758
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Membranes and Synaptosomes Used to Investigate Synaptic GABAergic Currents in Epileptic Patients.

    Gaeta, Alessandro / Lissner, Lilian Juliana / Alfano, Veronica / Cifelli, Pierangelo / Morano, Alessandra / Roseti, Cristina / Di Iacovo, Angela / Aronica, Eleonora / Palma, Eleonora / Ruffolo, Gabriele

    Membranes

    2024  Volume 14, Issue 3

    Abstract: Among the most prevalent neurological disorders, epilepsy affects about 1% of the population worldwide. We previously found, using human epileptic tissues, that GABAergic neurotransmission impairment is a key mechanism that drives the pathological ... ...

    Abstract Among the most prevalent neurological disorders, epilepsy affects about 1% of the population worldwide. We previously found, using human epileptic tissues, that GABAergic neurotransmission impairment is a key mechanism that drives the pathological phenomena that ultimately lead to generation and recurrence of seizures. Using both a "microtransplantation technique" and synaptosomes preparations from drug-resistant temporal lobe epilepsies (TLEs), we used the technique of two-electrode voltage clamp to record GABA-evoked currents, focusing selectively on the synaptic "fast inhibition" mediated by low-affinity GABA
    Language English
    Publishing date 2024-03-02
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2614641-1
    ISSN 2077-0375
    ISSN 2077-0375
    DOI 10.3390/membranes14030064
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: Editorial: Epilepsy and Neurodevelopmental Diseases.

    Ruffolo, Gabriele / Van Vliet, Erwin A / Aronica, Eleonora / Palma, Eleonora

    Frontiers in cellular neuroscience

    2020  Volume 14, Page(s) 255

    Language English
    Publishing date 2020-09-25
    Publishing country Switzerland
    Document type Editorial
    ZDB-ID 2452963-1
    ISSN 1662-5102
    ISSN 1662-5102
    DOI 10.3389/fncel.2020.00255
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: An Unbalanced Synaptic Transmission: Cause or Consequence of the Amyloid Oligomers Neurotoxicity?

    Sciaccaluga, Miriam / Megaro, Alfredo / Bellomo, Giovanni / Ruffolo, Gabriele / Romoli, Michele / Palma, Eleonora / Costa, Cinzia

    International journal of molecular sciences

    2021  Volume 22, Issue 11

    Abstract: Amyloid-β (Aβ) 1-40 and 1-42 peptides are key mediators of synaptic and cognitive dysfunction in Alzheimer's disease (AD). Whereas in AD, Aβ is found to act as a pro-epileptogenic factor even before plaque formation, amyloid pathology has been detected ... ...

    Abstract Amyloid-β (Aβ) 1-40 and 1-42 peptides are key mediators of synaptic and cognitive dysfunction in Alzheimer's disease (AD). Whereas in AD, Aβ is found to act as a pro-epileptogenic factor even before plaque formation, amyloid pathology has been detected among patients with epilepsy with increased risk of developing AD. Among Aβ aggregated species, soluble oligomers are suggested to be responsible for most of Aβ's toxic effects. Aβ oligomers exert extracellular and intracellular toxicity through different mechanisms, including interaction with membrane receptors and the formation of ion-permeable channels in cellular membranes. These damages, linked to an unbalance between excitatory and inhibitory neurotransmission, often result in neuronal hyperexcitability and neural circuit dysfunction, which in turn increase Aβ deposition and facilitate neurodegeneration, resulting in an Aβ-driven vicious loop. In this review, we summarize the most representative literature on the effects that oligomeric Aβ induces on synaptic dysfunction and network disorganization.
    MeSH term(s) Alzheimer Disease/genetics ; Alzheimer Disease/metabolism ; Alzheimer Disease/pathology ; Amyloid beta-Peptides/adverse effects ; Amyloid beta-Peptides/genetics ; Amyloid beta-Peptides/ultrastructure ; Amyloidogenic Proteins/adverse effects ; Amyloidogenic Proteins/genetics ; Animals ; Humans ; Peptide Fragments/genetics ; Peptide Fragments/metabolism ; Protein Multimerization/genetics ; Synapses/genetics ; Synapses/metabolism ; Synaptic Transmission/genetics
    Chemical Substances Amyloid beta-Peptides ; Amyloidogenic Proteins ; Peptide Fragments
    Language English
    Publishing date 2021-06-01
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms22115991
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article: Effects of 3,4-diaminopyridine on myasthenia gravis: Preliminary results of an open-label study.

    Ceccanti, Marco / Libonati, Laura / Ruffolo, Gabriele / Cifelli, Pierangelo / Moret, Federica / Frasca, Vittorio / Palma, Eleonora / Inghilleri, Maurizio / Cambieri, Chiara

    Frontiers in pharmacology

    2022  Volume 13, Page(s) 982434

    Abstract: Background: ...

    Abstract Background:
    Language English
    Publishing date 2022-08-16
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2587355-6
    ISSN 1663-9812
    ISSN 1663-9812
    DOI 10.3389/fphar.2022.982434
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article: GABAergic Neurotransmission in Human Tissues Is Modulated by Cannabidiol.

    Ruffolo, Gabriele / Gaeta, Alessandro / Cannata, Beatrice / Pinzaglia, Camilla / Aronica, Eleonora / Morano, Alessandra / Cifelli, Pierangelo / Palma, Eleonora

    Life (Basel, Switzerland)

    2022  Volume 12, Issue 12

    Abstract: Recently, the potential use of phytocannabinoids (pCBs) to treat different pathological conditions has attracted great attention in the scientific community. Among the different pCBs, cannabidiol (CBD) has showed interesting biological properties, making ...

    Abstract Recently, the potential use of phytocannabinoids (pCBs) to treat different pathological conditions has attracted great attention in the scientific community. Among the different pCBs, cannabidiol (CBD) has showed interesting biological properties, making it a promising molecule with a high security profile that has been approved for treatment as an add-on therapy in patients afflicted by severe pharmaco-resistant epilepsy, including Dravet syndrome (DS), Lennox-Gastaut syndrome (LGS) and tuberous sclerosis complex (TSC). CBD is pharmacologically considered a "dirty drug", since it has the capacity to bind different targets and to activate several cellular pathways. GABAergic impairment is one of the key processes during the epileptogenesis period able to induce a generalized hyperexcitability of the central nervous system (CNS), leading to epileptic seizures. Here, by using the microtransplantation of human brain membranes approach in
    Language English
    Publishing date 2022-12-06
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2662250-6
    ISSN 2075-1729
    ISSN 2075-1729
    DOI 10.3390/life12122042
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Lipid mediator n-3 docosapentaenoic acid-derived protectin D1 enhances synaptic inhibition of hippocampal principal neurons by interaction with a G-protein-coupled receptor.

    Mikroulis, Apostolos / Ledri, Marco / Ruffolo, Gabriele / Palma, Eleonora / Sperk, Günther / Dalli, Jesmond / Vezzani, Annamaria / Kokaia, Merab

    FASEB journal : official publication of the Federation of American Societies for Experimental Biology

    2022  Volume 36, Issue 3, Page(s) e22203

    Abstract: Epilepsy is a severe neurological disease manifested by spontaneous recurrent seizures due to abnormal hyper-synchronization of neuronal activity. Epilepsy affects about 1% of the population and up to 40% of patients experience seizures that are ... ...

    Abstract Epilepsy is a severe neurological disease manifested by spontaneous recurrent seizures due to abnormal hyper-synchronization of neuronal activity. Epilepsy affects about 1% of the population and up to 40% of patients experience seizures that are resistant to currently available drugs, thus highlighting an urgent need for novel treatments. In this regard, anti-inflammatory drugs emerged as potential therapeutic candidates. In particular, specific molecules apt to resolve the neuroinflammatory response occurring in acquired epilepsies have been proven to counteract seizures in experimental models, and humans. One candidate investigational molecule has been recently identified as the lipid mediator n-3 docosapentaenoic acid-derived protectin D1 (PD1
    MeSH term(s) Animals ; CA1 Region, Hippocampal/cytology ; CA1 Region, Hippocampal/metabolism ; CA1 Region, Hippocampal/physiology ; Docosahexaenoic Acids/pharmacology ; Inhibitory Postsynaptic Potentials ; Mice ; Mice, Inbred C57BL ; Neurons/drug effects ; Neurons/metabolism ; Neurons/physiology ; Receptors, Cell Surface/metabolism ; Xenopus
    Chemical Substances Receptors, Cell Surface ; pertussis toxin receptor ; protectin D1 ; Docosahexaenoic Acids (25167-62-8)
    Language English
    Publishing date 2022-03-22
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 639186-2
    ISSN 1530-6860 ; 0892-6638
    ISSN (online) 1530-6860
    ISSN 0892-6638
    DOI 10.1096/fj.202101815R
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 2266: Show issues Location:
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    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)
    Zs.MO 296: Show issues

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  9. Article ; Online: Impaired GABAergic regulation and developmental immaturity in interneurons derived from the medial ganglionic eminence in the tuberous sclerosis complex.

    Scheper, Mirte / Sørensen, Frederik N F / Ruffolo, Gabriele / Gaeta, Alessandro / Lissner, Lilian J / Anink, Jasper J / Korshunova, Irina / Jansen, Floor E / Riney, Kate / van Hecke, Wim / Mühlebner, Angelika / Khodosevich, Konstantin / Schubert, Dirk / Palma, Eleonora / Mills, James D / Aronica, Eleonora

    Acta neuropathologica

    2024  Volume 147, Issue 1, Page(s) 80

    Abstract: GABAergic interneurons play a critical role in maintaining neural circuit balance, excitation-inhibition regulation, and cognitive function modulation. In tuberous sclerosis complex (TSC), GABAergic neuron dysfunction contributes to disrupted network ... ...

    Abstract GABAergic interneurons play a critical role in maintaining neural circuit balance, excitation-inhibition regulation, and cognitive function modulation. In tuberous sclerosis complex (TSC), GABAergic neuron dysfunction contributes to disrupted network activity and associated neurological symptoms, assumingly in a cell type-specific manner. This GABAergic centric study focuses on identifying specific interneuron subpopulations within TSC, emphasizing the unique characteristics of medial ganglionic eminence (MGE)- and caudal ganglionic eminence (CGE)-derived interneurons. Using single-nuclei RNA sequencing in TSC patient material, we identify somatostatin-expressing (SST+) interneurons as a unique and immature subpopulation in TSC. The disrupted maturation of SST+ interneurons may undergo an incomplete switch from excitatory to inhibitory GABAergic signaling during development, resulting in reduced inhibitory properties. Notably, this study reveals markers of immaturity specifically in SST+ interneurons, including an abnormal NKCC1/KCC2 ratio, indicating an imbalance in chloride homeostasis crucial for the postsynaptic consequences of GABAergic signaling as well as the downregulation of GABA
    MeSH term(s) Interneurons/pathology ; Interneurons/metabolism ; Tuberous Sclerosis/pathology ; Tuberous Sclerosis/metabolism ; Humans ; GABAergic Neurons/pathology ; GABAergic Neurons/metabolism ; Male ; Female ; Median Eminence/pathology ; Median Eminence/metabolism ; Somatostatin/metabolism ; Child ; Child, Preschool ; Receptors, GABA-A/metabolism ; Adolescent ; Ganglionic Eminence
    Chemical Substances Somatostatin (51110-01-1) ; Receptors, GABA-A
    Language English
    Publishing date 2024-05-07
    Publishing country Germany
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1079-0
    ISSN 1432-0533 ; 0001-6322
    ISSN (online) 1432-0533
    ISSN 0001-6322
    DOI 10.1007/s00401-024-02737-7
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Ui II Zs.188: Show issues Location:
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  10. Article ; Online: Intranasal Administration of KYCCSRK Peptide Rescues Brain Insulin Signaling Activation and Reduces Alzheimer’s Disease-like Neuropathology in a Mouse Model for Down Syndrome

    Tramutola, Antonella / Lanzillotta, Simona / Aceto, Giuseppe / Pagnotta, Sara / Ruffolo, Gabriele / Cifelli, Pierangelo / Marini, Federico / Ripoli, Cristian / Palma, Eleonora / Grassi, Claudio / Di Domenico, Fabio / Perluigi, Marzia / Barone, Eugenio

    Antioxidants. 2023 Jan. 02, v. 12, no. 1

    2023  

    Abstract: Down syndrome (DS) is the most frequent genetic cause of intellectual disability and is strongly associated with Alzheimer’s disease (AD). Brain insulin resistance greatly contributes to AD development in the general population and previous studies from ... ...

    Abstract Down syndrome (DS) is the most frequent genetic cause of intellectual disability and is strongly associated with Alzheimer’s disease (AD). Brain insulin resistance greatly contributes to AD development in the general population and previous studies from our group showed an early accumulation of insulin resistance markers in DS brain, already in childhood, and even before AD onset. Here we tested the effects promoted in Ts2Cje mice by the intranasal administration of the KYCCSRK peptide known to foster insulin signaling activation by directly interacting and activating the insulin receptor (IR) and the AKT protein. Therefore, the KYCCSRK peptide might represent a promising molecule to overcome insulin resistance. Our results show that KYCCSRK rescued insulin signaling activation, increased mitochondrial complexes levels (OXPHOS) and reduced oxidative stress levels in the brain of Ts2Cje mice. Moreover, we uncovered novel characteristics of the KYCCSRK peptide, including its efficacy in reducing DYRK1A (triplicated in DS) and BACE1 protein levels, which resulted in reduced AD-like neuropathology in Ts2Cje mice. Finally, the peptide elicited neuroprotective effects by ameliorating synaptic plasticity mechanisms that are altered in DS due to the imbalance between inhibitory vs. excitatory currents. Overall, our results represent a step forward in searching for new molecules useful to reduce intellectual disability and counteract AD development in DS.
    Keywords Down syndrome ; brain ; childhood ; insulin ; insulin receptors ; insulin resistance ; intranasal administration ; mice ; mitochondria ; models ; neuropathology ; neuroplasticity ; oxidative stress ; peptides
    Language English
    Dates of publication 2023-0102
    Publishing place Multidisciplinary Digital Publishing Institute
    Document type Article ; Online
    ZDB-ID 2704216-9
    ISSN 2076-3921
    ISSN 2076-3921
    DOI 10.3390/antiox12010111
    Database NAL-Catalogue (AGRICOLA)

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