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  1. Article ; Online: Imaging of brain barrier inflammation and brain fluid drainage in human neurological diseases.

    Okar, Serhat V / Fagiani, Francesca / Absinta, Martina / Reich, Daniel S

    Cellular and molecular life sciences : CMLS

    2024  Volume 81, Issue 1, Page(s) 31

    Abstract: The intricate relationship between the central nervous system (CNS) and the immune system plays a crucial role in the pathogenesis of various neurological diseases. Understanding the interactions among the immunopathological processes at the brain ... ...

    Abstract The intricate relationship between the central nervous system (CNS) and the immune system plays a crucial role in the pathogenesis of various neurological diseases. Understanding the interactions among the immunopathological processes at the brain borders is essential for advancing our knowledge of disease mechanisms and developing novel diagnostic and therapeutic approaches. In this review, we explore the emerging role of neuroimaging in providing valuable insights into brain barrier inflammation and brain fluid drainage in human neurological diseases. Neuroimaging techniques have enabled us not only to visualize and assess brain structures, but also to study the dynamics of the CNS in health and disease in vivo. By analyzing imaging findings, we can gain a deeper understanding of the immunopathology observed at the brain-immune interface barriers, which serve as critical gatekeepers that regulate immune cell trafficking, cytokine release, and clearance of waste products from the brain. This review explores the integration of neuroimaging data with immunopathological findings, providing valuable insights into brain barrier integrity and immune responses in neurological diseases. Such integration may lead to the development of novel diagnostic markers and targeted therapeutic approaches that can benefit patients with neurological disorders.
    MeSH term(s) Humans ; Glymphatic System/pathology ; Brain/pathology ; Central Nervous System/pathology ; Nervous System Diseases/diagnostic imaging ; Nervous System Diseases/therapy ; Nervous System Diseases/pathology ; Inflammation/diagnostic imaging ; Inflammation/pathology ; Blood-Brain Barrier/diagnostic imaging
    Language English
    Publishing date 2024-01-12
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 1358415-7
    ISSN 1420-9071 ; 1420-682X
    ISSN (online) 1420-9071
    ISSN 1420-682X
    DOI 10.1007/s00018-023-05073-3
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: The Fuzzy Border between the Functional and Dysfunctional Effects of Beta-Amyloid: A Synaptocentric View of Neuron-Glia Entanglement.

    Fagiani, Francesca / Fulop, Tamas / Govoni, Stefano / Lanni, Cristina

    Biomedicines

    2023  Volume 11, Issue 2

    Abstract: Recent observations from clinical trials using monoclonal antibodies against Aβ seem to suggest that Aβ-targeting is modestly effective and not sufficiently based on an effective challenge of the role of Aβ from physiological to pathological. After an ... ...

    Abstract Recent observations from clinical trials using monoclonal antibodies against Aβ seem to suggest that Aβ-targeting is modestly effective and not sufficiently based on an effective challenge of the role of Aβ from physiological to pathological. After an accelerated approval procedure for aducanumab, and more recently lecanemab, their efficacy and safety remain to be fully defined despite previous attempts with various monoclonal antibodies, and both academic institutions and pharmaceutical companies are actively searching for novel treatments. Aβ needs to be clarified further in a more complicated context, taking into account both its accumulation and its biological functions during the course of the disease. In this review, we discuss the border between activities affecting early, potentially reversible dysfunctions of the synapse and events trespassing the threshold of inflammatory, self-sustaining glial activation, leading to irreversible damage. We detail a clear understanding of the biological mechanisms underlying the derangement from function to dysfunction and the switch of the of Aβ role from physiological to pathological. A picture is emerging where the optimal therapeutic strategy against AD should involve a number of allied molecular processes, displaying efficacy not only in reducing the well-known AD pathogenesis players, such as Aβ or neuroinflammation, but also in preventing their adverse effects.
    Language English
    Publishing date 2023-02-08
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2720867-9
    ISSN 2227-9059
    ISSN 2227-9059
    DOI 10.3390/biomedicines11020484
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: The Frailty Puzzle: Searching for Immortality or for Knowledge Survival?

    Govoni, Stefano / Fagiani, Francesca / Lanni, Cristina / Allegri, Nicola

    Frontiers in cellular neuroscience

    2022  Volume 16, Page(s) 838447

    Abstract: What is the value of assessing the biological age and frailty and predicting residual lifespan and health status? The benefit is obvious if we have means to alter the pace of aging and the development of frailty. So far, limited but increasing examples ... ...

    Abstract What is the value of assessing the biological age and frailty and predicting residual lifespan and health status? The benefit is obvious if we have means to alter the pace of aging and the development of frailty. So far, limited but increasing examples of interventions altering the predicted status indicate that, at least in some cases, this is possible through interventions spanning from the economic-social through drug treatments. Thus, why searching for biological markers, when some clinical and socio-economic indicators do already provide sufficiently accurate predictions? Indeed, the search of frailty biomarkers and of their biological clocks helps to build up a mechanistic frame that may orientate the design of interventions and the time window of their efficacy. Among the candidate biomarkers identified, several studies converge to indicate epigenetic clocks as a promising sensitive biomarker of the aging process. Moreover, it will help to establish the relationship between personal aging and health trajectories and to individuate the check points beyond which biological changes are irreversible.
    Language English
    Publishing date 2022-02-17
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2452963-1
    ISSN 1662-5102
    ISSN 1662-5102
    DOI 10.3389/fncel.2022.838447
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Book ; Online ; Thesis: Dectin-2: the C-type lectin receptor governs neutrophils by cooperating with Fcγ receptor IV to drive neutrophil-mediated skin inflammation

    Fagiani, Francesca [Verfasser] / Sadik, Christian [Akademischer Betreuer] / Manz, Rudolf [Akademischer Betreuer]

    2023  

    Author's details Francesca Fagiani ; Akademische Betreuer: Christian Sadik, Rudolf Manz
    Keywords Naturwissenschaften ; Science
    Subject code sg500
    Language English
    Publisher Zentrale Hochschulbibliothek Lübeck
    Publishing place Lübeck
    Document type Book ; Online ; Thesis
    Database Digital theses on the web

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  5. Article: (Dys)regulation of Synaptic Activity and Neurotransmitter Release by β-Amyloid: A Look Beyond Alzheimer's Disease Pathogenesis.

    Fagiani, Francesca / Lanni, Cristina / Racchi, Marco / Govoni, Stefano

    Frontiers in molecular neuroscience

    2021  Volume 14, Page(s) 635880

    Abstract: Beside its widely studied role in the pathogenesis of Alzheimer's disease (AD), β-amyloid (Aβ) is a normal and soluble product of neuronal metabolism that regulates several key physiological functions, exerting neuromodulatory effects on synaptic ... ...

    Abstract Beside its widely studied role in the pathogenesis of Alzheimer's disease (AD), β-amyloid (Aβ) is a normal and soluble product of neuronal metabolism that regulates several key physiological functions, exerting neuromodulatory effects on synaptic plasticity, memory, and neurotransmitter release. Such effects have been observed to occur in a hormetic fashion, with Aβ exhibiting a dual role influenced by its concentration, the different isoforms, or aggregation forms of the peptide. However, to date, our knowledge about the physiological functions of Aβ and, in particular, its modulatory role on synaptic activity and neurotransmission in the normal brain is fragmentary, thus hindering a clear comprehension of the biological mechanisms underlying the derangement from function to dysfunction. In particular, according to the amyloid cascade hypothesis, the switch from physiology to pathology is linked to the abnormal increase in Aβ levels, due to an imbalance in Aβ production and clearance. In this regard, increased Aβ levels have been hypothesized to induce early defects in synaptic function and such alterations have been suggested to account, at least in part, for the onset of neuropsychiatric symptoms (e.g., apathy, anxiety, changes in mood, depression, and agitation/aggression), frequently observed in the prodromal stage of AD. Therefore, understanding the biological mechanisms underlying early synaptic alterations in AD is a key starting point to frame the relevant time windows for AD treatment and to gain insight into AD etiopathogenesis.
    Language English
    Publishing date 2021-02-24
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2452967-9
    ISSN 1662-5099
    ISSN 1662-5099
    DOI 10.3389/fnmol.2021.635880
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Molecular features of IGHV3-53-encoded antibodies elicited by SARS-CoV-2.

    Fagiani, Francesca / Catanzaro, Michele / Lanni, Cristina

    Signal transduction and targeted therapy

    2020  Volume 5, Issue 1, Page(s) 170

    MeSH term(s) Antibody Formation ; Betacoronavirus ; COVID-19 ; Coronavirus Infections ; Humans ; Pandemics ; Pneumonia, Viral ; SARS-CoV-2
    Keywords covid19
    Language English
    Publishing date 2020-08-25
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Comment
    ZDB-ID 2886872-9
    ISSN 2059-3635 ; 2095-9907
    ISSN (online) 2059-3635
    ISSN 2095-9907
    DOI 10.1038/s41392-020-00287-4
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Targeting dementias through cancer kinases inhibition.

    Fagiani, Francesca / Lanni, Cristina / Racchi, Marco / Govoni, Stefano

    Alzheimer's & dementia (New York, N. Y.)

    2020  Volume 6, Issue 1, Page(s) e12044

    Abstract: The failures in Alzheimer's disease (AD) therapy strongly suggest the importance of reconsidering the research strategies analyzing other mechanisms that may take place in AD as well as, in general, in other neurodegenerative dementias. Taking into ... ...

    Abstract The failures in Alzheimer's disease (AD) therapy strongly suggest the importance of reconsidering the research strategies analyzing other mechanisms that may take place in AD as well as, in general, in other neurodegenerative dementias. Taking into account that in AD a variety of defects result in neurotransmitter activity and signaling efficiency imbalance, neuronal cell degeneration and defects in damage/repair systems, aberrant and abortive cell cycle, glial dysfunction, and neuroinflammation, a target may be represented by the intracellular signaling machinery provided by the kinome. In particular, based on the observations of a relationship between cancer and AD, we focused on cancer kinases for targeting neurodegeneration, highlighting the importance of targeting the intracellular pathways at the intersection between cell metabolism control/duplication, the inhibition of which may stop a progression in neurodegeneration.
    Language English
    Publishing date 2020-07-08
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2832891-7
    ISSN 2352-8737 ; 2352-8737
    ISSN (online) 2352-8737
    ISSN 2352-8737
    DOI 10.1002/trc2.12044
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: The Peptidyl-prolyl Isomerase Pin1 in Neuronal Signaling: from Neurodevelopment to Neurodegeneration.

    Fagiani, Francesca / Govoni, Stefano / Racchi, Marco / Lanni, Cristina

    Molecular neurobiology

    2020  Volume 58, Issue 3, Page(s) 1062–1073

    Abstract: The peptidyl-prolyl isomerase Pin1 is a unique enzyme catalyzing the isomerization of the peptide bond between phosphorylated serine-proline or threonine-proline motifs in proteins, thereby regulating a wide spectrum of protein functions, including ... ...

    Abstract The peptidyl-prolyl isomerase Pin1 is a unique enzyme catalyzing the isomerization of the peptide bond between phosphorylated serine-proline or threonine-proline motifs in proteins, thereby regulating a wide spectrum of protein functions, including folding, intracellular signaling, transcription, cell cycle progression, and apoptosis. Pin1 has been reported to act as a key molecular switch inducing cell-type-specific effects, critically depending on the different phosphorylation patterns of its targets within different biological contexts. While its implication in proliferating cells, and, in particular, in the field of cancer, has been widely characterized, less is known about Pin1 biological functions in terminally differentiated and post-mitotic neurons. Notably, Pin1 is widely expressed in the central and peripheral nervous system, where it regulates a variety of neuronal processes, including neuronal development, apoptosis, and synaptic activity. However, despite studies reporting the interaction of Pin1 with neuronal substrates or its involvement in specific signaling pathways, a more comprehensive understanding of its biological functions at neuronal level is still lacking. Besides its implication in physiological processes, a growing body of evidence suggests the crucial involvement of Pin1 in aging and age-related and neurodegenerative diseases, including Alzheimer's disease, Parkinson disease, frontotemporal dementias, Huntington disease, and amyotrophic lateral sclerosis, where it mediates profoundly different effects, ranging from neuroprotective to neurotoxic. Therefore, a more detailed understanding of Pin1 neuronal functions may provide relevant information on the consequences of Pin1 deregulation in age-related and neurodegenerative disorders.
    MeSH term(s) Aging/pathology ; Animals ; Humans ; NIMA-Interacting Peptidylprolyl Isomerase/metabolism ; Nerve Degeneration/enzymology ; Nerve Degeneration/pathology ; Nervous System/embryology ; Neurons/enzymology ; Neurons/pathology ; Signal Transduction
    Chemical Substances NIMA-Interacting Peptidylprolyl Isomerase
    Language English
    Publishing date 2020-10-21
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 645020-9
    ISSN 1559-1182 ; 0893-7648
    ISSN (online) 1559-1182
    ISSN 0893-7648
    DOI 10.1007/s12035-020-02179-8
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article: The Circadian Molecular Machinery in CNS Cells: A Fine Tuner of Neuronal and Glial Activity With Space/Time Resolution.

    Fagiani, Francesca / Baronchelli, Eva / Pittaluga, Anna / Pedrini, Edoardo / Scacchi, Chiara / Govoni, Stefano / Lanni, Cristina

    Frontiers in molecular neuroscience

    2022  Volume 15, Page(s) 937174

    Abstract: The circadian molecular machinery is a fine timekeeper with the capacity to harmonize physiological and behavioral processes with the external environment. This tight-knit regulation is coordinated by multiple cellular clocks across the body. In this ... ...

    Abstract The circadian molecular machinery is a fine timekeeper with the capacity to harmonize physiological and behavioral processes with the external environment. This tight-knit regulation is coordinated by multiple cellular clocks across the body. In this review, we focus our attention on the molecular mechanisms regulated by the clock in different brain areas and within different cells of the central nervous system. Further, we discuss evidence regarding the role of circadian rhythms in the regulation of neuronal activity and neurotransmitter systems. Not only neurons, but also astrocytes and microglia actively participate in the maintenance of timekeeping within the brain, and the diffusion of circadian information among these cells is fine-tuned by neurotransmitters (e.g., dopamine, serotonin, and γ-aminobutyric acid), thus impacting on the core clock machinery. The bidirectional interplay between neurotransmitters and the circadian clockwork is fundamental in maintaining accuracy and precision in daily timekeeping throughout different brain areas. Deepening the knowledge of these correlations allows us to define the basis of drug interventions to restore circadian rhythms, as well as to predict the onset of drug treatment/side effects that might promote daily desynchronization. Furthermore, it may lead to a deeper understanding of the potential impacts of modulations in rhythmic activities on the pace of aging and provide an insight in to the pathogenesis of psychiatric diseases and neurodegenerative disorders.
    Language English
    Publishing date 2022-07-01
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2452967-9
    ISSN 1662-5099
    ISSN 1662-5099
    DOI 10.3389/fnmol.2022.937174
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Double Attack to Oxidative Stress in Neurodegenerative Disorders: MAO-B and Nrf2 as Elected Targets.

    Basagni, Filippo / Di Paolo, Maria Luisa / Cozza, Giorgio / Dalla Via, Lisa / Fagiani, Francesca / Lanni, Cristina / Rosini, Michela / Minarini, Anna

    Molecules (Basel, Switzerland)

    2023  Volume 28, Issue 21

    Abstract: Oxidative stress and neuroinflammation play a pivotal role in triggering the neurodegenerative pathological cascades which characterize neurodegenerative disorders, such as Alzheimer's and Parkinson's diseases. In search for potential efficient ... ...

    Abstract Oxidative stress and neuroinflammation play a pivotal role in triggering the neurodegenerative pathological cascades which characterize neurodegenerative disorders, such as Alzheimer's and Parkinson's diseases. In search for potential efficient treatments for these pathologies, that are still considered unmet medical needs, we started from the promising properties of the antidiabetic drug pioglitazone, which has been repositioned as an MAO-B inhibitor, characterized by promising neuroprotective properties. Herein, with the aim to broaden its neuroprotective profile, we tried to enrich pioglitazone with direct and indirect antioxidant properties by hanging polyphenolic and electrophilic features that are able to trigger Nrf2 pathway and the resulting cytoprotective genes' transcription, as well as serve as radical scavengers. After a preliminary screening on MAO-B inhibitory properties, caffeic acid derivative
    MeSH term(s) Humans ; Antioxidants/pharmacology ; Antioxidants/metabolism ; NF-E2-Related Factor 2/metabolism ; Pioglitazone/pharmacology ; Oxidative Stress ; Neurodegenerative Diseases/metabolism ; Monoamine Oxidase/metabolism
    Chemical Substances Antioxidants ; NF-E2-Related Factor 2 ; Pioglitazone (X4OV71U42S) ; Monoamine Oxidase (EC 1.4.3.4)
    Language English
    Publishing date 2023-11-04
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 1413402-0
    ISSN 1420-3049 ; 1431-5165 ; 1420-3049
    ISSN (online) 1420-3049
    ISSN 1431-5165 ; 1420-3049
    DOI 10.3390/molecules28217424
    Database MEDical Literature Analysis and Retrieval System OnLINE

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