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Article: Schizophrenia and Glutathione: A Challenging Story.

Carletti, Barbara / Banaj, Nerisa / Piras, Fabrizio / Bossù, Paola

2023 Volume 13, Issue 11

Abstract: Schizophrenia (SZ) is a devastating mental illness with a complex and heterogeneous clinical state. Several conditions like symptoms, stage and severity of the disease are only some of the variables that have to be considered to define the disorder and ... ...

Abstract	Schizophrenia (SZ) is a devastating mental illness with a complex and heterogeneous clinical state. Several conditions like symptoms, stage and severity of the disease are only some of the variables that have to be considered to define the disorder and its phenotypes. SZ pathophysiology is still unclear, and the diagnosis is currently relegated to the analysis of clinical symptoms; therefore, the search for biomarkers with diagnostic relevance is a major challenge in the field, especially in the era of personalized medicine. Though the mechanisms implicated in SZ are not fully understood, some processes are beginning to be elucidated. Oxidative stress, and in particular glutathione (GSH) dysregulation, has been demonstrated to play a crucial role in SZ pathophysiology. In fact, glutathione is a leading actor of oxidative-stress-mediated damage in SZ and appears to reflect the heterogeneity of the disease. The literature reports differing results regarding the levels of glutathione in SZ patients. However, each GSH state may be a sign of specific symptoms or groups of symptoms, candidating glutathione as a biomarker useful for discriminating SZ phenotypes. Here, we summarize the literature about the levels of glutathione in SZ and analyze the role of this molecule and its potential use as a biomarker.
Language	English
Publishing date	2023-10-25
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2662248-8
ISSN	2075-4426
ISSN	2075-4426
DOI	10.3390/jpm13111526
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Cause or consequence? The role of IL-1 family cytokines and receptors in neuroinflammatory and neurodegenerative diseases.

Boraschi, Diana / Italiani, Paola / Migliorini, Paola / Bossù, Paola

Frontiers in immunology

2023 Volume 14, Page(s) 1128190

Abstract: Cytokines and receptors of the IL-1 family are key mediators in innate immune and inflammatory reactions in physiological defensive conditions, but are also significantly involved in immune-mediated inflammatory diseases. Here, we will address the role ... ...

Abstract	Cytokines and receptors of the IL-1 family are key mediators in innate immune and inflammatory reactions in physiological defensive conditions, but are also significantly involved in immune-mediated inflammatory diseases. Here, we will address the role of cytokines of the IL-1 superfamily and their receptors in neuroinflammatory and neurodegenerative diseases, in particular Multiple Sclerosis and Alzheimer's disease. Notably, several members of the IL-1 family are present in the brain as tissue-specific splice variants. Attention will be devoted to understanding whether these molecules are involved in the disease onset or are effectors of the downstream degenerative events. We will focus on the balance between the inflammatory cytokines IL-1β and IL-18 and inhibitory cytokines and receptors, in view of future therapeutic approaches.
MeSH term(s)	Humans ; Cytokines ; Neurodegenerative Diseases ; Alzheimer Disease ; Inflammation ; Brain
Chemical Substances	Cytokines
Language	English
Publishing date	2023-05-08
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2023.1128190
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Article: Implication of Aging Related Chronic Neuroinflammation on COVID-19 Pandemic.

Bossù, Paola / Toppi, Elisa / Sterbini, Valentina / Spalletta, Gianfranco

Journal of personalized medicine

2020 Volume 10, Issue 3

Abstract: SARS-CoV-2, the virus responsible for the COVID-19 pandemic, leads to a respiratory syndrome and other manifestations. Most affected people show no or mild symptoms, but the risk of severe disease and death increases in older people. Here, we report a ... ...

Abstract	SARS-CoV-2, the virus responsible for the COVID-19 pandemic, leads to a respiratory syndrome and other manifestations. Most affected people show no or mild symptoms, but the risk of severe disease and death increases in older people. Here, we report a narrative review on selected studies targeting aging-related chronic neuroinflammation in the COVID-19 pandemic. A hyperactivation of the innate immune system with elevated levels of pro-inflammatory cytokines occurs during severe COVID-19, pointing to an important role of the innate immune dysregulation in the disease outcome. Aging is characterized by a general condition of low-grade inflammation, also connected to chronic inflammation of the brain (neuroinflammation), which is involved in frailty syndrome and contributes to several age-associated diseases, including neurodegenerative and neuropsychiatric disorders. Since neuroinflammation can be induced or worsened by the virus infection itself, as well as by stressful conditions like those linked to the recent pandemic, the role of neuroinflammatory mechanisms could be central in a vicious circle leading to an increase in the mortality risk in aged COVID-19 patients. Furthermore, triggered neuroinflammatory pathways and consequent neurodegenerative and neuropsychiatric conditions might be potential long-term complications of COVID-19. In order to provide insights to help clinicians in identifying patients who progress to a more severe case of the disease, this review underlines the potential implications of aging-related neuroinflammation in COVID-19 pandemic.
Keywords	covid19
Language	English
Publishing date	2020-08-26
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2662248-8
ISSN	2075-4426
ISSN	2075-4426
DOI	10.3390/jpm10030102
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Article: The Anti-SARS-CoV-2 Antibody Response in a Centenarian Woman: A Case of Long-Term Memory?

Toppi, Elisa / De Molfetta, Veronica / Zarletti, Gianpaolo / Tiberi, Massimo / Bossù, Paola / Scapigliati, Giuseppe

Viruses. 2021 Aug. 27, v. 13, no. 9

2021

Abstract: SARS-CoV-2 is the virus responsible for the COVID-19 pandemic, causing respiratory syndrome and other manifestations. The clinical consequences of the SARS-CoV-2 infection are highly heterogeneous, ranging from asymptomatic and mild to severe and fatal ... ...

Abstract	SARS-CoV-2 is the virus responsible for the COVID-19 pandemic, causing respiratory syndrome and other manifestations. The clinical consequences of the SARS-CoV-2 infection are highly heterogeneous, ranging from asymptomatic and mild to severe and fatal conditions, with the highest mortality rate reached among elderly people. Such heterogeneity appears strongly influenced by the host immune response, which in turn is profoundly affected by aging. In fact, the occurrence of a low-grade inflammation and a decline in specific immune defense is generally reported in older people. Although the low ability of B cells to provide primary and secondary specific responses with a consequent increase in susceptibility to and severity of virus infections is generally described in elderly people, we would like to present here the particular case of a 100-year-old woman, who recovered well from COVID-19 and developed a long-term memory against SARS-CoV-2. Following the infection, the patient’s blood was tested with both a classical ELISA and a specific Cell-ELISA addressed to measure the anti-spike S1 specific IgG released in plasma or produced in vitro by memory B cells, respectively. While showing negative on classical serological testing, the patient’s blood was positive in Cell-ELISA up to 1 year after the infection. Our observation highlights a potential mechanism of B cell-dependent, long-term protection in response to SARS-CoV-2 infection, suggesting that in a case of successful aging, the absence of specific antibodies in serum does not necessarily mean the absence of immune memory.
Keywords	COVID-19 infection ; Severe acute respiratory syndrome coronavirus 2 ; antibody formation ; blood serum ; elderly ; immunologic memory ; inflammation ; memory ; mortality ; patients ; viruses ; women
Language	English
Dates of publication	2021-0827
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
ZDB-ID	2516098-9
ISSN	1999-4915
ISSN	1999-4915
DOI	10.3390/v13091704
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: The Anti-SARS-CoV-2 Antibody Response in a Centenarian Woman: A Case of Long-Term Memory?

Toppi, Elisa / De Molfetta, Veronica / Zarletti, Gianpaolo / Tiberi, Massimo / Bossù, Paola / Scapigliati, Giuseppe

Viruses

2021 Volume 13, Issue 9

Abstract	SARS-CoV-2 is the virus responsible for the COVID-19 pandemic, causing respiratory syndrome and other manifestations. The clinical consequences of the SARS-CoV-2 infection are highly heterogeneous, ranging from asymptomatic and mild to severe and fatal conditions, with the highest mortality rate reached among elderly people. Such heterogeneity appears strongly influenced by the host immune response, which in turn is profoundly affected by aging. In fact, the occurrence of a low-grade inflammation and a decline in specific immune defense is generally reported in older people. Although the low ability of B cells to provide primary and secondary specific responses with a consequent increase in susceptibility to and severity of virus infections is generally described in elderly people, we would like to present here the particular case of a 100-year-old woman, who recovered well from COVID-19 and developed a long-term memory against SARS-CoV-2. Following the infection, the patient's blood was tested with both a classical ELISA and a specific Cell-ELISA addressed to measure the anti-spike S1 specific IgG released in plasma or produced in vitro by memory B cells, respectively. While showing negative on classical serological testing, the patient's blood was positive in Cell-ELISA up to 1 year after the infection. Our observation highlights a potential mechanism of B cell-dependent, long-term protection in response to SARS-CoV-2 infection, suggesting that in a case of successful aging, the absence of specific antibodies in serum does not necessarily mean the absence of immune memory.
MeSH term(s)	Age Factors ; Aged, 80 and over ; Antibodies, Viral/blood ; Antibodies, Viral/immunology ; Antibody Formation/immunology ; B-Lymphocytes/immunology ; B-Lymphocytes/metabolism ; COVID-19/blood ; COVID-19/diagnosis ; COVID-19/immunology ; COVID-19/virology ; Enzyme-Linked Immunosorbent Assay ; Female ; Host-Pathogen Interactions/immunology ; Humans ; Immunoglobulin G/blood ; Immunoglobulin G/immunology ; Immunologic Memory ; Radiography, Thoracic ; SARS-CoV-2/immunology
Chemical Substances	Antibodies, Viral ; Immunoglobulin G
Language	English
Publishing date	2021-08-27
Publishing country	Switzerland
Document type	Case Reports
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v13091704
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: IL-33 and IL-10 Serum Levels Increase in MCI Patients Following Homotaurine Treatment.

Toppi, Elisa / Sireno, Laura / Lembo, Micaela / Banaj, Nerisa / Messina, Beatrice / Golesorkhtafti, Sedigheh / Spalletta, Gianfranco / Bossù, Paola

Frontiers in immunology

2022 Volume 13, Page(s) 813951

Abstract: Homotaurine is a potential therapeutic compound for treatment of Alzheimer's disease (AD), but its efficacy is still under investigation. Emerging data have shown that other than neuroprotective, homotaurine is endowed with anti-inflammatory activities, ... ...

Abstract	Homotaurine is a potential therapeutic compound for treatment of Alzheimer's disease (AD), but its efficacy is still under investigation. Emerging data have shown that other than neuroprotective, homotaurine is endowed with anti-inflammatory activities, though with still unclear underlying mechanisms. Inflammation plays a critical role in the pathogenesis of AD and we previously suggested that homotaurine supplementation in patients with amnestic mild cognitive impairment (MCI) plays beneficial effects associated to a decrease in the circulating levels of the pro-inflammatory cytokine IL-18. Here we report that MCI patients supplemented with homotaurine for 12 months show elevated serum levels of IL-10 and IL-33, as compared to baseline, in addition to the described IL-18 decrease. Furthermore, we observed a significant positive correlation between IL-10 and IL-33 levels after treatment but not at the baseline, underlining the effectiveness of the compound in modulating both cytokines in an inter-related fashion and in regulating the pro/anti-inflammation balance. Furthermore, the elevation of both IL-10 and IL-33 is significantly associated with an improvement of episodic memory of treated patients, as measured by the Delayed Verbal Ray Test. In conclusion, our results confirm that homotaurine treatment exerts an overall anti-inflammatory action in MCI patients, based not only on the down-regulation of pro-inflammatory IL-18, but also on up-regulation of the anti-inflammatory IL-33 and IL-10 cytokines, which in turn are associated with an amelioration of patient's cognitive functions. Future studies should be addressed to investigate the molecular mechanisms of homotaurine anti-inflammatory activity and its therapeutic exploitation in early AD.
MeSH term(s)	Alzheimer Disease/pathology ; Cognitive Dysfunction/drug therapy ; Cognitive Dysfunction/pathology ; Cytokines ; Humans ; Interleukin-10 ; Interleukin-18 ; Interleukin-33 ; Taurine/analogs & derivatives
Chemical Substances	Cytokines ; Interleukin-18 ; Interleukin-33 ; Interleukin-10 (130068-27-8) ; Taurine (1EQV5MLY3D) ; tramiprosate (5K8EAX0G53)
Language	English
Publishing date	2022-04-19
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2022.813951
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Article ; Online: Is Innate Memory a Double-Edge Sword in Alzheimer's Disease? A Reappraisal of New Concepts and Old Data.

Salani, Francesca / Sterbini, Valentina / Sacchinelli, Eleonora / Garramone, Mariagrazia / Bossù, Paola

Frontiers in immunology

2019 Volume 10, Page(s) 1768

Abstract: An emergent concept in immunology suggests that innate immune system is capable to undergo non-specific long-term responses and to provide resistance by modifying the reactivity to sequential pathogen challenge. This phenomenon, named innate memory, ... ...

Abstract	An emergent concept in immunology suggests that innate immune system is capable to undergo non-specific long-term responses and to provide resistance by modifying the reactivity to sequential pathogen challenge. This phenomenon, named innate memory, involves epigenetic, and metabolic reprogramming of innate immune cells. Current literature shows that the innate memory process has a mainly beneficial role in host defense, but sometimes can exert detrimental effects, as common in many diseases. Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline and dementia. Accumulating findings demonstrate that inflammation is involved in AD pathogenesis and progression and recent genetic and functional data confirm the driving role of the innate immune component in the disease. Furthermore, AD patients show high burden of the most relevant infectious agents and up-regulation of inflammatory features in their innate immune cells, including an activated, or "primed" status of myeloid phagocytic cells in both brain and periphery, resembling trained immunity conditions. Thus, it is conceivable that AD innate cells may be firstly involved in the attempt to resolve recurrent/persistent inflammation but then acquire a trained phenotype mostly unable to maintain the immune regulation, leaving uncontrolled or sometimes supporting the progression of neurodegeneration. The present review aims to summarize evidence evoking innate immune memory mechanisms in AD, and to interpret their potential role, either protective or harmful, in disease progression. A better understanding of such mechanisms will provide a fertile ground for development of novel diagnostic, and therapeutic pathways in AD cure.
MeSH term(s)	Alzheimer Disease/diagnosis ; Alzheimer Disease/genetics ; Alzheimer Disease/immunology ; Alzheimer Disease/pathology ; Humans ; Immunity, Innate ; Immunologic Memory ; Inflammation/diagnosis ; Inflammation/genetics ; Inflammation/immunology ; Inflammation/pathology
Language	English
Publishing date	2019-08-07
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2019.01768
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Implication of Aging Related Chronic Neuroinflammation on COVID-19 Pandemic

Bossù, Paola / Toppi, Elisa / Sterbini, Valentina / Spalletta, Gianfranco

Abstract	SARS-CoV-2, the virus responsible for the COVID-19 pandemic, leads to a respiratory syndrome and other manifestations. Most affected people show no or mild symptoms, but the risk of severe disease and death increases in older people. Here, we report a narrative review on selected studies targeting aging-related chronic neuroinflammation in the COVID-19 pandemic. A hyperactivation of the innate immune system with elevated levels of pro-inflammatory cytokines occurs during severe COVID-19, pointing to an important role of the innate immune dysregulation in the disease outcome. Aging is characterized by a general condition of low-grade inflammation, also connected to chronic inflammation of the brain (neuroinflammation), which is involved in frailty syndrome and contributes to several age-associated diseases, including neurodegenerative and neuropsychiatric disorders. Since neuroinflammation can be induced or worsened by the virus infection itself, as well as by stressful conditions like those linked to the recent pandemic, the role of neuroinflammatory mechanisms could be central in a vicious circle leading to an increase in the mortality risk in aged COVID-19 patients. Furthermore, triggered neuroinflammatory pathways and consequent neurodegenerative and neuropsychiatric conditions might be potential long-term complications of COVID-19. In order to provide insights to help clinicians in identifying patients who progress to a more severe case of the disease, this review underlines the potential implications of aging-related neuroinflammation in COVID-19 pandemic.
Keywords	covid19
Publisher	WHO
Document type	Article
Note	WHO #Covidence: #730853
Database	COVID19

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Article: A Cell-Based ELISA to Improve the Serological Analysis of Anti-SARS-CoV-2 IgG

Zarletti, Gianpaolo / Tiberi, Massimo / De Molfetta, Veronica / Bossù, Maurizio / Toppi, Elisa / Bossù, Paola / Scapigliati, Giuseppe

Viruses. 2020 Nov. 08, v. 12, no. 11

2020

Abstract: Knowledge of the antibody-mediated immune response to SARS-CoV-2 is crucial to understand virus immunogenicity, establish seroprevalence, and determine whether subjects or recovered patients are at risk for infection/reinfection and would therefore ... ...

Abstract	Knowledge of the antibody-mediated immune response to SARS-CoV-2 is crucial to understand virus immunogenicity, establish seroprevalence, and determine whether subjects or recovered patients are at risk for infection/reinfection and would therefore benefit from vaccination. Here, we describe a novel and simple cell-ELISA specifically designed to measure viral spike S1-specific IgG produced in vitro by B cells in peripheral blood mononuclear cell (PBMC) cultures from a cohort of 45 asymptomatic (n = 24) and symptomatic (n = 21) individuals, with age ranging from 8 to 99 years. All subjects underwent ELISA serological screening twice, at the same time as the cell-ELISA (T2) as well as 35–60 days earlier (T1). Cryopreserved PBMCs of healthy donors obtained years before the COVID-19 pandemic were also included in the analysis. The preliminary results presented here show that out of 45 tested subjects, 16 individuals (35.5%) were positive to the cell-ELISA, 11 (24.5%) were concomitantly positive in the serological screening (T1 and/or T2), and only one person was exclusively positive in ELISA (T1) and negative in cell-ELISA, though values were close to the cutoff. Of note, five individuals (11.2%) tested negative in ELISA but positive in cell-ELISA and thus, they appear to have circulating B cells that produce antibodies against SARS-CoV-2, likely at levels that are undetectable in the serum, which challenges the negative results of the serological screening. The relative level of in vitro secreted IgG was measurable in positive subjects, ranging from 7 to 50 ng/well. Accordingly, all anti-SARS-CoV-2 antibody-positive subjects previously reported moderate to severe symptoms attributable to COVID-19, even though the RT-PCR data were rarely available to confirm viral infection. Overall, the described cell-ELISA might be an effective method for detecting subjects who encountered the virus in the past, and thus helpful to improve serological ELISA tests in the case of undetectable/equivocal circulating IgG levels, and a suitable and improved tool to better evaluate SARS-CoV-2-specific humoral immunity in the COVID-19 pandemic.
Keywords	B-lymphocytes ; COVID-19 infection ; Severe acute respiratory syndrome coronavirus 2 ; antibodies ; blood serum ; cryopreservation ; enzyme-linked immunosorbent assay ; humoral immunity ; immune response ; immunogenicity ; immunoglobulin G ; patients ; reverse transcriptase polymerase chain reaction ; risk ; screening ; serodiagnosis ; seroprevalence ; vaccination ; viruses
Language	English
Dates of publication	2020-1108
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
ZDB-ID	2516098-9
ISSN	1999-4915
ISSN	1999-4915
DOI	10.3390/v12111274
Database	NAL-Catalogue (AGRICOLA)

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Article: Myeloid Dendritic Cells are Potential Players in Human Neurodegenerative Diseases.

Bossù, Paola / Spalletta, Gianfranco / Caltagirone, Carlo / Ciaramella, Antonio

Frontiers in immunology

2015 Volume 6, Page(s) 632

Abstract: Alzheimer's diseases (AD) and Parkinson's diseases (PD) are devastating neurodegenerative disturbances, wherein neuroinflammation is a chronic pathogenic process with high therapeutic potential. Major mediators of AD/PD neuroimmune processes are resident ...

Abstract	Alzheimer's diseases (AD) and Parkinson's diseases (PD) are devastating neurodegenerative disturbances, wherein neuroinflammation is a chronic pathogenic process with high therapeutic potential. Major mediators of AD/PD neuroimmune processes are resident immune cells, but immune cells derived from periphery may also participate and to some extent modify neuroinflammation. Specifically, blood borne myeloid cells emerge as crucial components of AD/PD progression and susceptibility. Among these, dendritic cells (DCs) are key immune orchestrators and players of brain immune surveillance; we candidate them as potential mediators of both AD and PD and as relevant cell model for unraveling myeloid cell role in neurodegeneration. Hence, we recapitulate and discuss emerging data suggesting that blood-derived DCs play a role in experimental and human neurodegenerative diseases. In humans, in particular, DCs are modified by in vitro culture with neurodegeneration-associated pathogenic factors and dysregulated in AD patients, while the levels of DC precursors are decreased in AD and PD patients' blood, possibly as an index of their recruitment to the brain. Overall, we emphasize the need to explore the impact of DCs on neurodegeneration to uncover peripheral immune mechanisms of pathogenic importance, recognize potential biomarkers, and improve therapeutic approaches for neurodegenerative diseases.
Language	English
Publishing date	2015
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2606827-8
ISSN	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2015.00632
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