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  1. Article ; Online: p57kip2 nuclear export as a marker of oligodendrocytes differentiation: Towards an innovative phenotyping screening for the identification of myelin repair drugs.

    Monti, Barbara

    EBioMedicine

    2021  Volume 66, Page(s) 103298

    MeSH term(s) Active Transport, Cell Nucleus ; Myelin Sheath/metabolism ; Neurogenesis ; Oligodendroglia ; Pharmaceutical Preparations/metabolism
    Chemical Substances Pharmaceutical Preparations
    Language English
    Publishing date 2021-03-25
    Publishing country Netherlands
    Document type Journal Article ; Comment
    ZDB-ID 2851331-9
    ISSN 2352-3964
    ISSN (online) 2352-3964
    DOI 10.1016/j.ebiom.2021.103298
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Selection of suitable reference genes for gene expression studies in HMC3 cell line by quantitative real-time RT-PCR.

    Fazzina, Martina / Bergonzoni, Matteo / Massenzio, Francesca / Monti, Barbara / Frabetti, Flavia / Casadei, Raffaella

    Scientific reports

    2024  Volume 14, Issue 1, Page(s) 2431

    Abstract: Microglia represent the primary immune defense system within the central nervous system and play a role in the inflammatory processes occurring in numerous disorders, such as Parkinson's disease (PD). PD onset and progression are associated with factors ... ...

    Abstract Microglia represent the primary immune defense system within the central nervous system and play a role in the inflammatory processes occurring in numerous disorders, such as Parkinson's disease (PD). PD onset and progression are associated with factors considered possible causes of neuroinflammation, i.e. genetic mutations. In vitro models of microglial cells were established to identify specific molecular targets in PD through the analysis of gene expression data. Recently, the Human Microglial Clone 3 cell line (HMC3) has been characterized and a new human microglia model has emerged. Here we perform RT-qPCR analyses to evaluate the expression of ten reference genes in HMC3, untreated or stimulated to a pro-inflammatory status. The comparative ∆C
    MeSH term(s) Humans ; Microglia ; Reverse Transcriptase Polymerase Chain Reaction ; Gene Expression Profiling/methods ; Cell Line ; Real-Time Polymerase Chain Reaction/methods ; Gene Expression ; Clone Cells ; Reference Standards
    Language English
    Publishing date 2024-01-29
    Publishing country England
    Document type Journal Article
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-024-52415-7
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Histone post-translational modifications to target memory-related diseases.

    Monti, Barbara

    Current pharmaceutical design

    2013  Volume 19, Issue 28, Page(s) 5065–5075

    Abstract: Epigenetic mechanisms, i.e. the control gene of expression without changing DNA sequence, include DNA methylation, histone post-translational modifications (PTMs) and microRNAs (miRNAs). Aberrant epigenetic modifications are associated with several ... ...

    Abstract Epigenetic mechanisms, i.e. the control gene of expression without changing DNA sequence, include DNA methylation, histone post-translational modifications (PTMs) and microRNAs (miRNAs). Aberrant epigenetic modifications are associated with several pathological conditions, including brain diseases, resulting from environmental causes, ageing or genetic factors. The role of histone PTMs, including acetylation, phosphorylation, methylation and ubiquitylation, has been demonstrated in learning and memory, both in physiological conditions and in neuropathologies. Abnormalities in these modifications or in the machinery that control them are associated with several neurodegenerative, neuro-developmental and psychiatric diseases. Therefore, these epigenetic marks are promising targets to address memory-related diseases and strong efforts are presently focused on pharmacological and genetic approaches to this field.
    MeSH term(s) Acetylation/drug effects ; Animals ; Disease Models, Animal ; Enzyme Inhibitors/therapeutic use ; Hippocampus/drug effects ; Hippocampus/enzymology ; Hippocampus/metabolism ; Histones/metabolism ; Humans ; Memory Disorders/drug therapy ; Memory Disorders/enzymology ; Memory Disorders/metabolism ; Methylation/drug effects ; Molecular Targeted Therapy ; Nerve Tissue Proteins/antagonists & inhibitors ; Nerve Tissue Proteins/metabolism ; Neurodegenerative Diseases/drug therapy ; Neurodegenerative Diseases/enzymology ; Neurodegenerative Diseases/metabolism ; Neuronal Plasticity/drug effects ; Neurons/drug effects ; Neurons/enzymology ; Neurons/metabolism ; Nootropic Agents/therapeutic use ; Phosphorylation/drug effects ; Protein Processing, Post-Translational/drug effects
    Chemical Substances Enzyme Inhibitors ; Histones ; Nerve Tissue Proteins ; Nootropic Agents
    Language English
    Publishing date 2013-02-27
    Publishing country United Arab Emirates
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 1304236-1
    ISSN 1873-4286 ; 1381-6128
    ISSN (online) 1873-4286
    ISSN 1381-6128
    DOI 10.2174/1381612811319280005
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Microstructured soft devices for the growth and analysis of populations of homogenous multicellular tumor spheroids

    Tartagni, Ottavia / Borók, Alexandra / Mensà, Emanuela / Bonyár, Attila / Monti, Barbara / Hofkens, Johan / Porcelli, Anna Maria / Zuccheri, Giampaolo

    Cell. Mol. Life Sci.. 2023 Apr., v. 80, no. 4 p.93-93

    2023  

    Abstract: Multicellular tumor spheroids are rapidly emerging as an improved in vitro model with respect to more traditional 2D culturing. Microwell culturing is a simple and accessible method for generating a large number of uniformly sized spheroids, but ... ...

    Abstract Multicellular tumor spheroids are rapidly emerging as an improved in vitro model with respect to more traditional 2D culturing. Microwell culturing is a simple and accessible method for generating a large number of uniformly sized spheroids, but commercially available systems often do not enable researchers to perform complete culturing and analysis pipelines and the mechanical properties of their culture environment are not commonly matching those of the target tissue. We herein report a simple method to obtain custom-designed self-built microwell arrays made of polydimethylsiloxane or agarose for uniform 3D cell structure generation. Such materials can provide an environment of tunable mechanical flexibility. We developed protocols to culture a variety of cancer and non-cancer cell lines in such devices and to perform molecular and imaging characterizations of the spheroid growth, viability, and response to pharmacological treatments. Hundreds of tumor spheroids grow (in scaffolded or scaffold-free conditions) at homogeneous rates and can be harvested at will. Microscopy imaging can be performed in situ during or at the end of the culture. Fluorescence (confocal) microscopy can be performed after in situ staining while retaining the geographic arrangement of spheroids in the plate wells. This platform can enable statistically robust investigations on cancer biology and screening of drug treatments.
    Keywords agarose ; cell structures ; drugs ; fluorescence ; microscopy ; models ; neoplasms ; polydimethylsiloxane ; viability
    Language English
    Dates of publication 2023-04
    Size p. 93.
    Publishing place Springer International Publishing
    Document type Article ; Online
    ZDB-ID 1358415-7
    ISSN 1420-9071 ; 1420-682X
    ISSN (online) 1420-9071
    ISSN 1420-682X
    DOI 10.1007/s00018-023-04748-1
    Database NAL-Catalogue (AGRICOLA)

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  5. Article: New models of Parkinson's like neuroinflammation in human microglia clone 3: Activation profiles induced by INF-γ plus high glucose and mitochondrial inhibitors.

    De Chirico, Francesca / Poeta, Eleonora / Babini, Giorgia / Piccolino, Iliana / Monti, Barbara / Massenzio, Francesca

    Frontiers in cellular neuroscience

    2022  Volume 16, Page(s) 1038721

    Abstract: Microglia activation and neuroinflammation have been extensively studied in murine models of neurodegenerative diseases; however, to overcome the genetic differences between species, a human cell model of microglia able to recapitulate the activation ... ...

    Abstract Microglia activation and neuroinflammation have been extensively studied in murine models of neurodegenerative diseases; however, to overcome the genetic differences between species, a human cell model of microglia able to recapitulate the activation profiles described in patients is needed. Here we developed human models of Parkinson's like neuroinflammation by using the human microglia clone 3 (HMC3) cells, whose activation profile in response to classic inflammatory stimuli has been controversial and reported only at mRNA levels so far. In fact, we showed the increased expression of the pro-inflammatory markers iNOS, Caspase 1, IL-1β, in response to IFN-γ plus high glucose, a non-specific disease stimulus that emphasized the dynamic polarization and heterogenicity of the microglial population. More specifically, we demonstrated the polarization of HMC3 cells through the upregulation of iNOS expression and nitrite production in response to the Parkinson's like stimuli, 6-hydroxidopamine (6-OHDA) and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), the latter depending on the NF-κB pathway. Furthermore, we identified inflammatory mediators that promote the pro-inflammatory activation of human microglia as function of different pathways that can simulate the phenotypic transition according to the stage of the pathology. In conclusion, we established and characterized different systems of HMC3 cells activation as
    Language English
    Publishing date 2022-11-29
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2452963-1
    ISSN 1662-5102
    ISSN 1662-5102
    DOI 10.3389/fncel.2022.1038721
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Microstructured soft devices for the growth and analysis of populations of homogenous multicellular tumor spheroids.

    Tartagni, Ottavia / Borók, Alexandra / Mensà, Emanuela / Bonyár, Attila / Monti, Barbara / Hofkens, Johan / Porcelli, Anna Maria / Zuccheri, Giampaolo

    Cellular and molecular life sciences : CMLS

    2023  Volume 80, Issue 4, Page(s) 93

    Abstract: Multicellular tumor spheroids are rapidly emerging as an improved in vitro model with respect to more traditional 2D culturing. Microwell culturing is a simple and accessible method for generating a large number of uniformly sized spheroids, but ... ...

    Abstract Multicellular tumor spheroids are rapidly emerging as an improved in vitro model with respect to more traditional 2D culturing. Microwell culturing is a simple and accessible method for generating a large number of uniformly sized spheroids, but commercially available systems often do not enable researchers to perform complete culturing and analysis pipelines and the mechanical properties of their culture environment are not commonly matching those of the target tissue. We herein report a simple method to obtain custom-designed self-built microwell arrays made of polydimethylsiloxane or agarose for uniform 3D cell structure generation. Such materials can provide an environment of tunable mechanical flexibility. We developed protocols to culture a variety of cancer and non-cancer cell lines in such devices and to perform molecular and imaging characterizations of the spheroid growth, viability, and response to pharmacological treatments. Hundreds of tumor spheroids grow (in scaffolded or scaffold-free conditions) at homogeneous rates and can be harvested at will. Microscopy imaging can be performed in situ during or at the end of the culture. Fluorescence (confocal) microscopy can be performed after in situ staining while retaining the geographic arrangement of spheroids in the plate wells. This platform can enable statistically robust investigations on cancer biology and screening of drug treatments.
    MeSH term(s) Humans ; Spheroids, Cellular ; Neoplasms ; Cell Line ; Cell Line, Tumor
    Language English
    Publishing date 2023-03-16
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 1358415-7
    ISSN 1420-9071 ; 1420-682X
    ISSN (online) 1420-9071
    ISSN 1420-682X
    DOI 10.1007/s00018-023-04748-1
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Transcriptional and metabolic effects of aspartate-glutamate carrier isoform 1 (AGC1) downregulation in mouse oligodendrocyte precursor cells (OPCs).

    Balboni, Nicola / Babini, Giorgia / Poeta, Eleonora / Protti, Michele / Mercolini, Laura / Magnifico, Maria Chiara / Barile, Simona Nicole / Massenzio, Francesca / Pignataro, Antonella / Giorgi, Federico M / Lasorsa, Francesco Massimo / Monti, Barbara

    Cellular & molecular biology letters

    2024  Volume 29, Issue 1, Page(s) 44

    Abstract: Aspartate-glutamate carrier isoform 1 (AGC1) is a carrier responsible for the export of mitochondrial aspartate in exchange for cytosolic glutamate and is part of the malate-aspartate shuttle, essential for the balance of reducing equivalents in the ... ...

    Abstract Aspartate-glutamate carrier isoform 1 (AGC1) is a carrier responsible for the export of mitochondrial aspartate in exchange for cytosolic glutamate and is part of the malate-aspartate shuttle, essential for the balance of reducing equivalents in the cells. In the brain, mutations in SLC25A12 gene, encoding for AGC1, cause an ultra-rare genetic disease, reported as a neurodevelopmental encephalopathy, whose symptoms include global hypomyelination, arrested psychomotor development, hypotonia and seizures. Among the biological components most affected by AGC1 deficiency are oligodendrocytes, glial cells responsible for myelination processes, and their precursors [oligodendrocyte progenitor cells (OPCs)]. The AGC1 silencing in an in vitro model of OPCs was documented to cause defects of proliferation and differentiation, mediated by alterations of histone acetylation/deacetylation. Disrupting AGC1 activity could possibly reduce the availability of acetyl groups, leading to perturbation of many biological pathways, such as histone modifications and fatty acids formation for myelin production. Here, we explore the transcriptome of mouse OPCs partially silenced for AGC1, reporting results of canonical analyses (differential expression) and pathway enrichment analyses, which highlight a disruption in fatty acids synthesis from both a regulatory and enzymatic stand. We further investigate the cellular effects of AGC1 deficiency through the identification of most affected transcriptional networks and altered alternative splicing. Transcriptional data were integrated with differential metabolite abundance analysis, showing downregulation of several amino acids, including glutamine and aspartate. Taken together, our results provide a molecular foundation for the effects of AGC1 deficiency in OPCs, highlighting the molecular mechanisms affected and providing a list of actionable targets to mitigate the effects of this pathology.
    MeSH term(s) Mice ; Animals ; Down-Regulation/genetics ; Oligodendrocyte Precursor Cells/metabolism ; Aspartic Acid/metabolism ; Protein Isoforms/metabolism ; Fatty Acids ; Amino Acid Transport Systems, Acidic/deficiency ; Antiporters/deficiency ; Hereditary Central Nervous System Demyelinating Diseases ; Psychomotor Disorders ; Mitochondrial Diseases
    Chemical Substances aspartate-glutamate carrier ; Aspartic Acid (30KYC7MIAI) ; Protein Isoforms ; Fatty Acids ; Amino Acid Transport Systems, Acidic ; Antiporters
    Language English
    Publishing date 2024-03-29
    Publishing country England
    Document type Journal Article
    ZDB-ID 2108724-6
    ISSN 1689-1392 ; 1689-1392
    ISSN (online) 1689-1392
    ISSN 1689-1392
    DOI 10.1186/s11658-024-00563-z
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Coumarin-azasugar-benzyl conjugates as non-neurotoxic dual inhibitors of butyrylcholinesterase and cancer cell growth.

    Vaaland Holmgard, I Caroline / González-Bakker, Aday / Poeta, Eleonora / Puerta, Adrián / Fernandes, Miguel X / Monti, Barbara / Fernández-Bolaños, José G / Padrón, José M / López, Óscar / Lindbäck, Emil

    Organic & biomolecular chemistry

    2024  Volume 22, Issue 17, Page(s) 3425–3438

    Abstract: We have applied the copper-catalyzed azide-alkyne cycloaddition (CuAAC) reaction to prepare a library of ten coumarin-azasugar-benzyl conjugates and two phthalimide-azasugar-benzyl conjugates with potential anti-Alzheimer and anti-cancer properties. The ... ...

    Abstract We have applied the copper-catalyzed azide-alkyne cycloaddition (CuAAC) reaction to prepare a library of ten coumarin-azasugar-benzyl conjugates and two phthalimide-azasugar-benzyl conjugates with potential anti-Alzheimer and anti-cancer properties. The compounds were evaluated as cholinesterase inhibitors, demonstrating a general preference, of up to 676-fold, for the inhibition of butyrylcholinesterase (BuChE) over acetylcholinesterase (AChE). Nine of the compounds behaved as stronger BuChE inhibitors than galantamine, one of the few drugs in clinical use against Alzheimer's disease. The most potent BuChE inhibitor (IC
    MeSH term(s) Coumarins/chemistry ; Coumarins/pharmacology ; Coumarins/chemical synthesis ; Butyrylcholinesterase/metabolism ; Humans ; Cholinesterase Inhibitors/pharmacology ; Cholinesterase Inhibitors/chemistry ; Cholinesterase Inhibitors/chemical synthesis ; Cell Proliferation/drug effects ; Antineoplastic Agents/pharmacology ; Antineoplastic Agents/chemistry ; Antineoplastic Agents/chemical synthesis ; Animals ; Cell Line, Tumor ; Structure-Activity Relationship ; Molecular Structure ; Drug Screening Assays, Antitumor ; Aza Compounds/chemistry ; Aza Compounds/pharmacology ; Aza Compounds/chemical synthesis ; Dose-Response Relationship, Drug ; Neurons/drug effects
    Chemical Substances Coumarins ; Butyrylcholinesterase (EC 3.1.1.8) ; Cholinesterase Inhibitors ; Antineoplastic Agents ; coumarin (A4VZ22K1WT) ; Aza Compounds
    Language English
    Publishing date 2024-05-01
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2097583-1
    ISSN 1477-0539 ; 1477-0520
    ISSN (online) 1477-0539
    ISSN 1477-0520
    DOI 10.1039/d4ob00312h
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Targeting Lewy body dementia with neflamapimod-rasagiline hybrids.

    Albertini, Claudia / Petralla, Sabrina / Massenzio, Francesca / Monti, Barbara / Rizzardi, Nicola / Bergamini, Christian / Uliassi, Elisa / Borges, Fernanda / Chavarria, Daniel / Fricker, Gert / Goettert, Marcia / Kronenberger, Thales / Gehringer, Matthias / Laufer, Stefan / Bolognesi, Maria L

    Archiv der Pharmazie

    2024  , Page(s) e2300525

    Abstract: Lewy body dementia (LBD) represents the second most common neurodegenerative dementia but is a quite underexplored therapeutic area. Nepflamapimod (1) is a brain-penetrant selective inhibitor of the alpha isoform of the mitogen-activated serine/threonine ...

    Abstract Lewy body dementia (LBD) represents the second most common neurodegenerative dementia but is a quite underexplored therapeutic area. Nepflamapimod (1) is a brain-penetrant selective inhibitor of the alpha isoform of the mitogen-activated serine/threonine protein kinase (MAPK) p38α, recently repurposed for LBD due to its remarkable antineuroinflammatory properties. Neuroprotective propargylamines are another class of molecules with a therapeutical potential against LBD. Herein, we sought to combine the antineuroinflammatory core of 1 and the neuroprotective propargylamine moiety into a single molecule. Particularly, we inserted a propargylamine moiety in position 4 of the 2,6-dichlorophenyl ring of 1, generating neflamapimod-propargylamine hybrids 3 and 4. These hybrids were evaluated using several cell models, aiming to recapitulate the complexity of LBD pathology through different molecular mechanisms. The N-methyl-N-propargyl derivative 4 showed a nanomolar p38α-MAPK inhibitory activity (IC
    Language English
    Publishing date 2024-02-27
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 6381-2
    ISSN 1521-4184 ; 0365-6233 ; 1437-1014
    ISSN (online) 1521-4184
    ISSN 0365-6233 ; 1437-1014
    DOI 10.1002/ardp.202300525
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Dual-Acting Small Molecules: Subtype-Selective Cannabinoid Receptor 2 Agonist/Butyrylcholinesterase Inhibitor Hybrids Show Neuroprotection in an Alzheimer's Disease Mouse Model.

    Spatz, Philipp / Steinmüller, Sophie A M / Tutov, Anna / Poeta, Eleonora / Morilleau, Axelle / Carles, Allison / Deventer, Marie H / Hofmann, Julian / Stove, Christophe P / Monti, Barbara / Maurice, Tangui / Decker, Michael

    Journal of medicinal chemistry

    2023  Volume 66, Issue 9, Page(s) 6414–6435

    Abstract: We present the synthesis and characterization of merged human butyrylcholinesterase ( ...

    Abstract We present the synthesis and characterization of merged human butyrylcholinesterase (
    MeSH term(s) Animals ; Mice ; Humans ; Butyrylcholinesterase/metabolism ; Alzheimer Disease/drug therapy ; Neuroprotection ; Cholinesterase Inhibitors/pharmacology ; Cholinesterase Inhibitors/therapeutic use ; Cholinesterase Inhibitors/chemistry ; Receptors, Cannabinoid ; Acetylcholinesterase/metabolism ; Structure-Activity Relationship
    Chemical Substances Butyrylcholinesterase (EC 3.1.1.8) ; Cholinesterase Inhibitors ; Receptors, Cannabinoid ; Acetylcholinesterase (EC 3.1.1.7)
    Language English
    Publishing date 2023-04-26
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 218133-2
    ISSN 1520-4804 ; 0022-2623
    ISSN (online) 1520-4804
    ISSN 0022-2623
    DOI 10.1021/acs.jmedchem.3c00541
    Database MEDical Literature Analysis and Retrieval System OnLINE

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