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  1. Article ; Online: Innovative Therapies and Nanomedicine Applications for the Treatment of Alzheimer's Disease: A State-of-the-Art (2017-2020).

    Binda, Anna / Murano, Carmen / Rivolta, Ilaria

    International journal of nanomedicine

    2020  Volume 15, Page(s) 6113–6135

    Abstract: The field of nanomedicine is constantly expanding. Since the first work dated in 1999, almost 28 thousand articles have been published, and more and more are published every year: just think that only in the last five years 20,855 have come out (source ... ...

    Abstract The field of nanomedicine is constantly expanding. Since the first work dated in 1999, almost 28 thousand articles have been published, and more and more are published every year: just think that only in the last five years 20,855 have come out (source PUBMED) including original research and reviews. The goal of this review is to present the current knowledge about nanomedicine in Alzheimer's disease, a widespread neurodegenerative disorder in the over 60 population that deeply affects memory and cognition. Thus, after a brief introduction on the pathology and on the state-of-the-art research for NPs passing the BBB, special attention is placed to new targets that can enter the interest of nanoparticle designers and to new promising therapies. The authors performed a literature review limited to the last three years (2017-2020) of available studies with the intention to present only novel formulations or approaches where at least in vitro studies have been performed. This choice was made because, while limiting the sector to nanotechnology applied to Alzheimer, an organic census of all the relevant news is difficult to obtain.
    MeSH term(s) Alzheimer Disease/drug therapy ; Alzheimer Disease/physiopathology ; Animals ; Blood-Brain Barrier/drug effects ; Blood-Brain Barrier/physiology ; Drug Carriers/therapeutic use ; Drug Delivery Systems/methods ; Humans ; Nanomedicine/methods ; Nanoparticles/administration & dosage ; Nanoparticles/therapeutic use ; Precision Medicine ; Stem Cell Transplantation ; Theranostic Nanomedicine/methods ; Therapies, Investigational
    Chemical Substances Drug Carriers
    Language English
    Publishing date 2020-08-14
    Publishing country New Zealand
    Document type Journal Article ; Review
    ZDB-ID 2364941-0
    ISSN 1178-2013 ; 1176-9114
    ISSN (online) 1178-2013
    ISSN 1176-9114
    DOI 10.2147/IJN.S231480
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Caveolin-3 and Caveolin-1 Interaction Decreases Channel Dysfunction Due to Caveolin-3 Mutations.

    Benzoni, Patrizia / Gazzerro, Elisabetta / Fiorillo, Chiara / Baratto, Serena / Bartolucci, Chiara / Severi, Stefano / Milanesi, Raffaella / Lippi, Melania / Langione, Marianna / Murano, Carmen / Meoni, Clarissa / Popolizio, Vera / Cospito, Alessandro / Baruscotti, Mirko / Bucchi, Annalisa / Barbuti, Andrea

    International journal of molecular sciences

    2024  Volume 25, Issue 2

    Abstract: Caveolae constitute membrane microdomains where receptors and ion channels functionally interact. Caveolin-3 (cav-3) is the key structural component of muscular caveolae. Mutations ... ...

    Abstract Caveolae constitute membrane microdomains where receptors and ion channels functionally interact. Caveolin-3 (cav-3) is the key structural component of muscular caveolae. Mutations in
    MeSH term(s) Adult ; Animals ; Cricetinae ; Humans ; Caveolin 1/genetics ; Caveolin 3/genetics ; Cricetulus ; Mutation ; CHO Cells ; Ion Channels
    Chemical Substances Caveolin 1 ; Caveolin 3 ; Ion Channels
    Language English
    Publishing date 2024-01-12
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms25020980
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Effect of the ketogenic diet in excitable tissues.

    Murano, Carmen / Binda, Anna / Palestini, Paola / Baruscotti, Mirko / DiFrancesco, Jacopo C / Rivolta, Ilaria

    American journal of physiology. Cell physiology

    2021  Volume 320, Issue 4, Page(s) C547–C553

    Abstract: In the past decade, ketogenic diet (KD) has gained some popularity as a potential treatment for a wide range of diseases, including neurological and metabolic disorders, thanks to a beneficial role mainly related to its anti-inflammatory properties. The ... ...

    Abstract In the past decade, ketogenic diet (KD) has gained some popularity as a potential treatment for a wide range of diseases, including neurological and metabolic disorders, thanks to a beneficial role mainly related to its anti-inflammatory properties. The high-fat and carbohydrate-restricted regimen causes changes in the metabolism, leading, through the β-oxidation of fatty acids, to the hepatic production of ketone bodies (KBs), which are used by many extrahepatic tissues as energy fuels. Once synthetized, KBs are delivered through the systemic circulation to all the tissues of the organism, where they play pleiotropic roles acting directly and indirectly on various targets, and among them ion channels and neurotransmitters. Moreover, they can operate as signaling metabolites and epigenetic modulators. Therefore, it is inappropriate to consider that the KD regimen can improve the patients' clinical condition simply by means of specific and localized effects; rather, it is more correct to think that KBs affect the organism as a whole. In this review, we tried to summarize the recent knowledge of the effects of KBs on various tissues, with a particular attention on the excitable ones, namely the nervous system, heart, and muscles.
    MeSH term(s) 3-Hydroxybutyric Acid/metabolism ; Animals ; Central Nervous System Diseases/diet therapy ; Central Nervous System Diseases/metabolism ; Central Nervous System Diseases/physiopathology ; Diet, Ketogenic/adverse effects ; Energy Metabolism ; Heart Diseases/diet therapy ; Heart Diseases/metabolism ; Heart Diseases/physiopathology ; Humans ; Membrane Potentials ; Muscle Fibers, Skeletal/metabolism ; Muscular Diseases/diet therapy ; Muscular Diseases/metabolism ; Muscular Diseases/physiopathology ; Myocytes, Cardiac/metabolism ; Neurons/metabolism ; Signal Transduction
    Chemical Substances 3-Hydroxybutyric Acid (TZP1275679)
    Language English
    Publishing date 2021-01-27
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 392098-7
    ISSN 1522-1563 ; 0363-6143
    ISSN (online) 1522-1563
    ISSN 0363-6143
    DOI 10.1152/ajpcell.00458.2020
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: A novel de novo HCN2 loss-of-function variant causing developmental and epileptic encephalopathy treated with a ketogenic diet.

    DiFrancesco, Jacopo C / Ragona, Francesca / Murano, Carmen / Frosio, Anthony / Melgari, Dario / Binda, Anna / Calamaio, Serena / Prevostini, Rachele / Mauri, Mario / Canafoglia, Laura / Castellotti, Barbara / Messina, Giuliana / Gellera, Cinzia / Previtali, Roberto / Veggiotti, Pierangelo / Milanesi, Raffaella / Barbuti, Andrea / Solazzi, Roberta / Freri, Elena /
    Granata, Tiziana / Rivolta, Ilaria

    Epilepsia

    2023  Volume 64, Issue 12, Page(s) e222–e228

    Abstract: Missense variants of hyperpolarization-activated, cyclic nucleotide-gated (HCN) ion channels cause variable phenotypes, ranging from mild generalized epilepsy to developmental and epileptic encephalopathy (DEE). Although variants of HCN1 are an ... ...

    Abstract Missense variants of hyperpolarization-activated, cyclic nucleotide-gated (HCN) ion channels cause variable phenotypes, ranging from mild generalized epilepsy to developmental and epileptic encephalopathy (DEE). Although variants of HCN1 are an established cause of DEE, those of HCN2 have been reported in generalized epilepsies. Here we describe the first case of DEE caused by the novel de novo heterozygous missense variant c.1379G>A (p.G460D) of HCN2. Functional characterization in transfected HEK293 cells and neonatal rat cortical neurons revealed that HCN2 p.G460D currents were strongly reduced compared to wild-type, consistent with a dominant negative loss-of-function effect. Immunofluorescence staining showed that mutant channels are retained within the cell and do not reach the membrane. Moreover, mutant HCN2 also affect HCN1 channels, by reducing the I
    MeSH term(s) Humans ; Rats ; Animals ; Potassium Channels/genetics ; Potassium Channels/metabolism ; Diet, Ketogenic ; HEK293 Cells ; Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels/genetics ; Epilepsy, Generalized/genetics ; Cyclic Nucleotide-Gated Cation Channels
    Chemical Substances Potassium Channels ; Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels ; Cyclic Nucleotide-Gated Cation Channels ; HCN2 protein, human
    Language English
    Publishing date 2023-10-07
    Publishing country United States
    Document type Case Reports ; Journal Article
    ZDB-ID 216382-2
    ISSN 1528-1167 ; 0013-9580
    ISSN (online) 1528-1167
    ISSN 0013-9580
    DOI 10.1111/epi.17777
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  5. Article ; Online: Modulation of the intrinsic neuronal excitability by multifunctional liposomes tailored for the treatment of Alzheimer's disease.

    Binda, Anna / Panariti, Alice / Barbuti, Andrea / Murano, Carmen / Dal Magro, Roberta / Masserini, Massimo / Re, Francesca / Rivolta, Ilaria

    International journal of nanomedicine

    2018  Volume 13, Page(s) 4059–4071

    Abstract: Purpose: Nanotechnologies turned out to be promising in the development of diagnostic and therapeutic approaches toward neurodegenerative disorders. However, only a very scant number of nanodevices until now proved to be effective on preclinical animal ... ...

    Abstract Purpose: Nanotechnologies turned out to be promising in the development of diagnostic and therapeutic approaches toward neurodegenerative disorders. However, only a very scant number of nanodevices until now proved to be effective on preclinical animal models. Although specific tests in vivo are available to assess the potential toxicity of these nanodevices on cognitive functions, those to evaluate their biosafety in vitro on neurons are still to be improved.
    Materials and methods: We utilized the patch-clamp technique on primary cultures of cortical neural cells isolated from neonatal rats, aiming to evaluate their electrical properties after the incubation with liposomes (mApoE-PA-LIPs), previously proved able to cross the blood-brain barrier and to be effective on mouse models of Alzheimer's disease (AD), both in the absence and in the presence of β-amyloid peptide oligomers.
    Results: Data show a high degree of biocompatibility, evaluated by lactate dehydrogenase (LDH) release and MTT assay, and the lack of cellular internalization. After the incubation with mApoE-PA-LIPs, neuronal membranes show an increase in the input resistance (from 724.14±76 MΩ in untreated population to 886.06±86 MΩ in the treated one), a reduction in the rheobase current (from 29.6±3 to 24.2±3 pA in untreated and treated, respectively), and an increase of the firing frequency, consistent with an ultimate increase in intrinsic excitability. Data obtained after co-incubation of mApoE-PA-LIPs with β-amyloid peptide oligomers suggest a retention of liposome efficacy.
    Conclusion: These data suggest the ability of liposomes to modulate neuronal electrical properties and are compatible with the previously demonstrated amelioration of cognitive functions induced by treatment of AD mice with liposomes. We conclude that this electrophysiological approach could represent a useful tool for nanomedicine to evaluate the effect of nanoparticles on intrinsic neuronal excitability.
    MeSH term(s) Action Potentials ; Alzheimer Disease/drug therapy ; Amyloid beta-Peptides/metabolism ; Animals ; Animals, Newborn ; Apolipoproteins E/metabolism ; Biocompatible Materials/chemistry ; Cell Survival ; Cells, Cultured ; Endocytosis ; Liposomes ; Male ; Mice ; Nanoparticles/chemistry ; Neurons/metabolism ; Phosphatidic Acids/chemistry ; Rats
    Chemical Substances Amyloid beta-Peptides ; Apolipoproteins E ; Biocompatible Materials ; Liposomes ; Phosphatidic Acids
    Language English
    Publishing date 2018-07-11
    Publishing country New Zealand
    Document type Journal Article
    ZDB-ID 2364941-0
    ISSN 1178-2013 ; 1176-9114
    ISSN (online) 1178-2013
    ISSN 1176-9114
    DOI 10.2147/IJN.S161563
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Gabapentin treatment in a patient with KCNQ2 developmental epileptic encephalopathy.

    Soldovieri, Maria Virginia / Freri, Elena / Ambrosino, Paolo / Rivolta, Ilaria / Mosca, Ilaria / Binda, Anna / Murano, Carmen / Ragona, Francesca / Canafoglia, Laura / Vannicola, Chiara / Solazzi, Roberta / Granata, Tiziana / Castellotti, Barbara / Messina, Giuliana / Gellera, Cinzia / Labalme, Audrey / Lesca, Gaetan / DiFrancesco, Jacopo C / Taglialatela, Maurizio

    Pharmacological research

    2020  Volume 160, Page(s) 105200

    Abstract: De novo variants in KCNQ2 encoding for Kv7.2 voltage-dependent neuronal potassium ( ... ...

    Abstract De novo variants in KCNQ2 encoding for Kv7.2 voltage-dependent neuronal potassium (K
    MeSH term(s) Age of Onset ; Animals ; Anticonvulsants/therapeutic use ; CHO Cells ; Carbamates/therapeutic use ; Cells, Cultured ; Child ; Cricetinae ; Cricetulus ; Electroencephalography ; Epilepsy/drug therapy ; Epilepsy/genetics ; Female ; Gabapentin/therapeutic use ; Humans ; KCNQ2 Potassium Channel/genetics ; Mutation ; Phenylenediamines/therapeutic use ; Precision Medicine ; Rats ; Treatment Outcome
    Chemical Substances Anticonvulsants ; Carbamates ; KCNQ2 Potassium Channel ; KCNQ2 protein, human ; Phenylenediamines ; ezogabine (12G01I6BBU) ; Gabapentin (6CW7F3G59X)
    Keywords covid19
    Language English
    Publishing date 2020-09-15
    Publishing country Netherlands
    Document type Case Reports ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1003347-6
    ISSN 1096-1186 ; 0031-6989 ; 1043-6618
    ISSN (online) 1096-1186
    ISSN 0031-6989 ; 1043-6618
    DOI 10.1016/j.phrs.2020.105200
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  7. Article ; Online: Generation of human induced pluripotent stem cells (EURACi001-A, EURACi002-A, EURACi003-A) from peripheral blood mononuclear cells of three patients carrying mutations in the CAV3 gene.

    Meraviglia, Viviana / Benzoni, Patrizia / Landi, Sara / Murano, Carmen / Langione, Marianna / Motta, Benedetta M / Baratto, Serena / Silipigni, Rosamaria / Di Segni, Marina / Pramstaller, Peter P / DiFrancesco, Dario / Gazzerro, Elisabetta / Barbuti, Andrea / Rossini, Alessandra

    Stem cell research

    2017  Volume 27, Page(s) 25–29

    Abstract: Caveolinopathies are a heterogeneous family of genetic pathologies arising from alterations of the caveolin-3 gene (CAV3), encoding for the isoform specifically constituting muscle caveolae. Here, by reprogramming peripheral blood mononuclear cells, we ... ...

    Abstract Caveolinopathies are a heterogeneous family of genetic pathologies arising from alterations of the caveolin-3 gene (CAV3), encoding for the isoform specifically constituting muscle caveolae. Here, by reprogramming peripheral blood mononuclear cells, we report the generation of induced pluripotent stem cells (iPSCs) from three patients carrying the ΔYTT deletion, T78K and W101C missense mutations in caveolin-3. iPSCs displayed normal karyotypes and all the features of pluripotent stem cells in terms of morphology, specific marker expression and ability to differentiate in vitro into the three germ layers. These lines thus represent a human cellular model to study the molecular basis of caveolinopathies. Resource table.
    MeSH term(s) Caveolin 3/genetics ; Caveolin 3/metabolism ; Cell Differentiation/genetics ; Cell Differentiation/physiology ; Cells, Cultured ; Cellular Reprogramming/genetics ; Cellular Reprogramming/physiology ; Flow Cytometry ; Humans ; Induced Pluripotent Stem Cells/cytology ; Induced Pluripotent Stem Cells/metabolism ; Karyotype ; Leukocytes, Mononuclear/cytology ; Leukocytes, Mononuclear/metabolism ; Mutation/genetics ; Mutation, Missense/genetics ; Reverse Transcriptase Polymerase Chain Reaction
    Chemical Substances Caveolin 3
    Language English
    Publishing date 2017-12-18
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 1876-7753
    ISSN (online) 1876-7753
    DOI 10.1016/j.scr.2017.12.012
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article: Gabapentin treatment in a patient with KCNQ2 developmental epileptic encephalopathy

    Soldovieri, Maria Virginia / Freri, Elena / Ambrosino, Paolo / Rivolta, Ilaria / Mosca, Ilaria / Binda, Anna / Murano, Carmen / Ragona, Francesca / Canafoglia, Laura / Vannicola, Chiara / Solazzi, Roberta / Granata, Tiziana / Castellotti, Barbara / Messina, Giuliana / Gellera, Cinzia / Labalme, Audrey / Lesca, Gaetan / DiFrancesco, Jacopo C / Taglialatela, Maurizio

    Pharmacol Res

    Abstract: De novo variants in KCNQ2 encoding for Kv7.2 voltage-dependent neuronal potassium (K+) channel subunits are associated with developmental epileptic encephalopathy (DEE). We herein describe the clinical and electroencephalographic (EEG) features of a ... ...

    Abstract De novo variants in KCNQ2 encoding for Kv7.2 voltage-dependent neuronal potassium (K+) channel subunits are associated with developmental epileptic encephalopathy (DEE). We herein describe the clinical and electroencephalographic (EEG) features of a child with early-onset DEE caused by the novel KCNQ2 p.G310S variant. In vitro experiments demonstrated that the mutation induces loss-of-function effects on the currents produced by channels incorporating mutant subunits; these effects were counteracted by the selective Kv7 opener retigabine and by gabapentin, a recently described Kv7 activator. Given these data, the patient started treatment with gabapentin, showing a rapid and sustained clinical and EEG improvement over the following months. Overall, these results suggest that gabapentin can be regarded as a precision therapy for DEEs due to KCNQ2 loss-of-function mutations.
    Keywords covid19
    Publisher WHO
    Document type Article
    Note WHO #Covidence: #32942014
    Database COVID19

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