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  1. Article ; Online: Looking to the Future of the Role of Macrophages and Extracellular Vesicles in Neuroinflammation in ALS.

    Carata, Elisabetta / Muci, Marco / Di Giulio, Simona / Mariano, Stefania / Panzarini, Elisa

    International journal of molecular sciences

    2023  Volume 24, Issue 14

    Abstract: Neuroinflammation is a common pathological feature of amyotrophic lateral sclerosis (ALS). Although scientific evidence to date does not allow defining neuroinflammation as an ALS trigger, its role in exacerbating motor neuron (MNs) degeneration and ... ...

    Abstract Neuroinflammation is a common pathological feature of amyotrophic lateral sclerosis (ALS). Although scientific evidence to date does not allow defining neuroinflammation as an ALS trigger, its role in exacerbating motor neuron (MNs) degeneration and disease progression is attracting research interest. Activated CNS (Central Nervous System) glial cells, proinflammatory peripheral and infiltrated T lymphocytes and monocytes/macrophages, as well as the immunoreactive molecules they release, represent the active players for the role of immune dysregulation enhancing neuroinflammation. The crosstalk between the peripheral and CNS immune cells significantly correlates with the survival of ALS patients since the modification of peripheral macrophages can downregulate inflammation at the periphery along the nerves and in the CNS. As putative vehicles for misfolded protein and inflammatory mediators between cells, extracellular vesicles (EVs) have also drawn particular attention in the field of ALS. Both CNS and peripheral immune cells release EVs, which are able to modulate the behavior of neighboring recipient cells; unfortunately, the mechanisms involved in EVs-mediated communication in neuroinflammation remain unclear. This review aims to synthesize the current literature regarding EV-mediated cell-to-cell communication in the brain under ALS, with a particular point of view on the role of peripheral macrophages in responding to inflammation to understand the biological process and exploit it for ALS management.
    MeSH term(s) Humans ; Amyotrophic Lateral Sclerosis/metabolism ; Neuroinflammatory Diseases ; Macrophages/metabolism ; Inflammation/metabolism ; Extracellular Vesicles/metabolism
    Language English
    Publishing date 2023-07-08
    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/ijms241411251
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Induction of Autophagy Promotes Clearance of RHO

    Intartaglia, Daniela / Giamundo, Giuliana / Naso, Federica / Nusco, Edoardo / Di Giulio, Simona / Salierno, Francesco Giuseppe / Polishchuk, Elena / Conte, Ivan

    Frontiers in aging neuroscience

    2022  Volume 14, Page(s) 878958

    Abstract: Autophagy is a critical metabolic process that acts as a major self-digestion and recycling pathway contributing to maintain cellular homeostasis. An emerging field of research supports the therapeutic modulation of autophagy for treating human ... ...

    Abstract Autophagy is a critical metabolic process that acts as a major self-digestion and recycling pathway contributing to maintain cellular homeostasis. An emerging field of research supports the therapeutic modulation of autophagy for treating human neurodegenerative disorders, in which toxic aggregates are accumulated in neurons. Our previous study identified Ezrin protein as an inhibitor of autophagy and lysosomal functions in the retina; thus, in turn, identifying it as a potential pharmacological target for increasing retinal cell clearance to treat inherited retinal dystrophies in which misfolded proteins have accumulated. This study aimed to verify the therapeutic inhibition of Ezrin to induce clearance of toxic aggregates in a mouse model for a dominant form of retinitis pigmentosa (i.e., RHO
    Language English
    Publishing date 2022-06-30
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2558898-9
    ISSN 1663-4365
    ISSN 1663-4365
    DOI 10.3389/fnagi.2022.878958
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Copper Dependent Modulation of α-Synuclein Phosphorylation in Differentiated SHSY5Y Neuroblastoma Cells.

    Greco, Marco / Spinelli, Chiara Carmela / De Riccardis, Lidia / Buccolieri, Alessandro / Di Giulio, Simona / Musarò, Debora / Pagano, Claudia / Manno, Daniela / Maffia, Michele

    International journal of molecular sciences

    2021  Volume 22, Issue 4

    Abstract: Copper (Cu) dyshomeostasis plays a pivotal role in several neuropathologies, such as Parkinson's disease (PD). Metal accumulation in the central nervous system (CNS) could result in loss-of-function of proteins involved in Cu metabolism and redox cycling, ...

    Abstract Copper (Cu) dyshomeostasis plays a pivotal role in several neuropathologies, such as Parkinson's disease (PD). Metal accumulation in the central nervous system (CNS) could result in loss-of-function of proteins involved in Cu metabolism and redox cycling, generating reactive oxygen species (ROS). Moreover, neurodegenerative disorders imply the presence of an excess of misfolded proteins known to lead to neuronal damage. In PD, Cu accumulates in the brain, binds α-synuclein, and initiates its aggregation. We assessed the correlation between neuronal differentiation, Cu homeostasis regulation, and α-synuclein phosphorylation. At this purpose, we used differentiated SHSY5Y neuroblastoma cells to reproduce some of the characteristics of the dopaminergic neurons. Here, we reported that differentiated cells expressed a significantly higher amount of a copper transporter protein 1 (CTR1), increasing the copper uptake. Cells also showed a significantly more phosphorylated form of α-synuclein, further increased by copper treatment, without modifications in α-synuclein levels. This effect depended on the upregulation of the polo-like kinase 2 (PLK2), whereas the levels of the relative protein phosphatase 2A (PP2A) remained unvaried. No changes in the oxidative state of the cells were identified. The Cu dependent alteration of α-synuclein phosphorylation pattern might potentially offer new opportunities for clinical intervention.
    MeSH term(s) Cell Differentiation/drug effects ; Cell Line, Tumor ; Cell Survival/drug effects ; Copper/metabolism ; Copper/pharmacology ; Copper Transport Proteins/genetics ; Copper Transport Proteins/metabolism ; Copper-Transporting ATPases/genetics ; Copper-Transporting ATPases/metabolism ; Humans ; Molecular Chaperones/genetics ; Molecular Chaperones/metabolism ; Neuroblastoma/metabolism ; Neuroblastoma/pathology ; Phosphorylation/drug effects ; Protein-Serine-Threonine Kinases/genetics ; Protein-Serine-Threonine Kinases/metabolism ; alpha-Synuclein/metabolism
    Chemical Substances ATOX1 protein, human ; Copper Transport Proteins ; Molecular Chaperones ; alpha-Synuclein ; Copper (789U1901C5) ; PLK2 protein, human (EC 2.7.11.-) ; Protein-Serine-Threonine Kinases (EC 2.7.11.1) ; ATP7A protein, human (EC 7.2.2.8) ; Copper-Transporting ATPases (EC 7.2.2.8)
    Language English
    Publishing date 2021-02-18
    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/ijms22042038
    Database MEDical Literature Analysis and Retrieval System OnLINE

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