LIVIVO - The Search Portal for Life Sciences

zur deutschen Oberfläche wechseln
Advanced search

Search results

Result 1 - 6 of total 6

Search options

  1. Article ; Online: The Potential Contribution of Dysfunctional RNA-Binding Proteins to the Pathogenesis of Neurodegeneration in Multiple Sclerosis and Relevant Models.

    Libner, Cole D / Salapa, Hannah E / Levin, Michael C

    International journal of molecular sciences

    2020  Volume 21, Issue 13

    Abstract: Neurodegeneration in multiple sclerosis (MS) is believed to underlie disease progression and permanent disability. Many mechanisms of neurodegeneration in MS have been proposed, such as mitochondrial dysfunction, oxidative stress, neuroinflammation, and ... ...

    Abstract Neurodegeneration in multiple sclerosis (MS) is believed to underlie disease progression and permanent disability. Many mechanisms of neurodegeneration in MS have been proposed, such as mitochondrial dysfunction, oxidative stress, neuroinflammation, and RNA-binding protein dysfunction. The purpose of this review is to highlight mechanisms of neurodegeneration in MS and its models, with a focus on RNA-binding protein dysfunction. Studying RNA-binding protein dysfunction addresses a gap in our understanding of the pathogenesis of MS, which will allow for novel therapies to be generated to attenuate neurodegeneration before irreversible central nervous system damage occurs.
    MeSH term(s) Animals ; Disease Progression ; Humans ; Multiple Sclerosis/complications ; Neurodegenerative Diseases/etiology ; Neurodegenerative Diseases/metabolism ; Neurodegenerative Diseases/pathology ; Oxidative Stress ; RNA-Binding Proteins/metabolism
    Chemical Substances RNA-Binding Proteins
    Language English
    Publishing date 2020-06-27
    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/ijms21134571
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  2. Article ; Online: hnRNP A1 dysfunction in oligodendrocytes contributes to the pathogenesis of multiple sclerosis.

    Jahanbazi Jahan-Abad, Ali / Salapa, Hannah E / Libner, Cole D / Thibault, Patricia A / Levin, Michael C

    Glia

    2022  Volume 71, Issue 3, Page(s) 633–647

    Abstract: Oligodendrocyte (OL) damage and death are prominent features of multiple sclerosis (MS) pathology, yet mechanisms contributing to OL loss are incompletely understood. Dysfunctional RNA binding proteins (RBPs), hallmarked by nucleocytoplasmic ... ...

    Abstract Oligodendrocyte (OL) damage and death are prominent features of multiple sclerosis (MS) pathology, yet mechanisms contributing to OL loss are incompletely understood. Dysfunctional RNA binding proteins (RBPs), hallmarked by nucleocytoplasmic mislocalization and altered expression, have been shown to result in cell loss in neurologic diseases, including in MS. Since we previously observed that the RBP heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) was dysfunctional in neurons in MS, we hypothesized that it might also contribute to OL pathology in MS and relevant models. We discovered that hnRNP A1 dysfunction is characteristic of OLs in MS brains. These findings were recapitulated in the experimental autoimmune encephalomyelitis (EAE) mouse model of MS, where hnRNP A1 dysfunction was characteristic of OLs, including oligodendrocyte precursor cells and mature OLs in which hnRNP A1 dysfunction correlated with demyelination. We also found that hnRNP A1 dysfunction was induced by IFNγ, indicating that inflammation influences hnRNP A1 function. To fully understand the effects of hnRNP A1 dysfunction on OLs, we performed siRNA knockdown of hnRNP A1, followed by RNA sequencing. RNA sequencing detected over 4000 differentially expressed transcripts revealing alterations to RNA metabolism, cell morphology, and programmed cell death pathways. We confirmed that hnRNP A1 knockdown was detrimental to OLs and induced apoptosis and necroptosis. Together, these data demonstrate a critical role for hnRNP A1 in proper OL functioning and survival and suggest a potential mechanism of OL damage and death in MS that involves hnRNP A1 dysfunction.
    MeSH term(s) Animals ; Mice ; Heterogeneous Nuclear Ribonucleoprotein A1/genetics ; Heterogeneous Nuclear Ribonucleoprotein A1/metabolism ; Multiple Sclerosis/pathology ; RNA-Binding Proteins/metabolism ; Encephalomyelitis, Autoimmune, Experimental ; RNA, Small Interfering
    Chemical Substances Heterogeneous Nuclear Ribonucleoprotein A1 ; RNA-Binding Proteins ; RNA, Small Interfering
    Language English
    Publishing date 2022-11-16
    Publishing country United States
    Document type Journal Article
    ZDB-ID 639414-0
    ISSN 1098-1136 ; 0894-1491
    ISSN (online) 1098-1136
    ISSN 0894-1491
    DOI 10.1002/glia.24300
    Database MEDical Literature Analysis and Retrieval System OnLINE

    Full text online

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.A 2345: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  3. Article ; Online: hnRNP A1 dysfunction alters RNA splicing and drives neurodegeneration in multiple sclerosis (MS).

    Salapa, Hannah E / Thibault, Patricia A / Libner, Cole D / Ding, Yulian / Clarke, Joseph-Patrick W E / Denomy, Connor / Hutchinson, Catherine / Abidullah, Hashim M / Austin Hammond, S / Pastushok, Landon / Vizeacoumar, Frederick S / Levin, Michael C

    Nature communications

    2024  Volume 15, Issue 1, Page(s) 356

    Abstract: Neurodegeneration is the primary driver of disease progression in multiple sclerosis (MS) resulting in permanent disability, creating an urgent need to discover its underlying mechanisms. Herein, we establish that dysfunction of the RNA binding protein ... ...

    Abstract Neurodegeneration is the primary driver of disease progression in multiple sclerosis (MS) resulting in permanent disability, creating an urgent need to discover its underlying mechanisms. Herein, we establish that dysfunction of the RNA binding protein heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) results in differential of binding to RNA targets causing alternative RNA splicing, which contributes to neurodegeneration in MS and its models. Using RNAseq of MS brains, we discovered differential expression and aberrant splicing of hnRNP A1 target RNAs involved in neuronal function and RNA homeostasis. We confirmed this in vivo in experimental autoimmune encephalomyelitis employing CLIPseq specific for hnRNP A1, where hnRNP A1 differentially binds and regulates RNA, including aberrantly spliced targets identified in human samples. Additionally, dysfunctional hnRNP A1 expression in neurons caused neurite loss and identical changes in splicing, corroborating hnRNP A1 dysfunction as a cause of neurodegeneration. Collectively, these data indicate hnRNP A1 dysfunction causes altered neuronal RNA splicing, resulting in neurodegeneration in MS.
    MeSH term(s) Humans ; Alternative Splicing ; Heterogeneous Nuclear Ribonucleoprotein A1/genetics ; Multiple Sclerosis/genetics ; RNA ; RNA Splicing/genetics
    Chemical Substances Heterogeneous Nuclear Ribonucleoprotein A1 ; RNA (63231-63-0) ; hnRNPA1 protein, human
    Language English
    Publishing date 2024-01-08
    Publishing country England
    Document type Journal Article
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-023-44658-1
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  4. Article ; Online: Dysfunctional RNA-binding protein biology and neurodegeneration in experimental autoimmune encephalomyelitis in female mice.

    Salapa, Hannah E / Libner, Cole D / Levin, Michael C

    Journal of neuroscience research

    2019  Volume 98, Issue 4, Page(s) 704–717

    Abstract: Altered stress granule (SG) and RNA-binding protein (RBP) biology have been shown to contribute to the pathogenesis of several neurodegenerative diseases, yet little is known about their role in multiple sclerosis (MS). Pathological features associated ... ...

    Abstract Altered stress granule (SG) and RNA-binding protein (RBP) biology have been shown to contribute to the pathogenesis of several neurodegenerative diseases, yet little is known about their role in multiple sclerosis (MS). Pathological features associated with dysfunctional RBPs include RBP mislocalization from its normal nuclear location to the cytoplasm and the formation of chronic SGs. We tested the hypothesis that altered SG and RBP biology might contribute to the neurodegeneration in experimental autoimmune encephalomyelitis (EAE). C57BL/6 female mice were actively immunized with MOG
    MeSH term(s) Animals ; DNA-Binding Proteins/metabolism ; Encephalomyelitis, Autoimmune, Experimental/metabolism ; Encephalomyelitis, Autoimmune, Experimental/pathology ; Female ; Gray Matter/metabolism ; Gray Matter/pathology ; Heterogeneous Nuclear Ribonucleoprotein A1/metabolism ; Mice, Inbred C57BL ; Multiple Sclerosis/metabolism ; Multiple Sclerosis/pathology ; Neurons/metabolism ; Neurons/pathology ; RNA-Binding Proteins/metabolism ; Spinal Cord/metabolism ; Spinal Cord/pathology ; Stress, Physiological
    Chemical Substances DNA-Binding Proteins ; Heterogeneous Nuclear Ribonucleoprotein A1 ; Hnrnpa1 protein, mouse ; RNA-Binding Proteins ; TDP-43 protein, mouse
    Language English
    Publishing date 2019-11-22
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 195324-2
    ISSN 1097-4547 ; 0360-4012
    ISSN (online) 1097-4547
    ISSN 0360-4012
    DOI 10.1002/jnr.24554
    Database MEDical Literature Analysis and Retrieval System OnLINE

    Full text online

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.A 1232: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  5. Article ; Online: Autoimmunity to a ribonucleoprotein drives neuron loss in multiple sclerosis models.

    Libner, Cole D / Salapa, Hannah E / Hutchinson, Catherine / Stang, Todd E / Thibault, Patricia A / Hammond, S Austin / Levin, Michael C

    Neurobiology of disease

    2022  Volume 170, Page(s) 105775

    Abstract: Neurodegeneration, the progressive loss or damage to neurons and axons, underlies permanent disability in multiple sclerosis (MS); yet its mechanisms are incompletely understood. Recent data indicates autoimmunity to several intraneuronal antigens, ... ...

    Abstract Neurodegeneration, the progressive loss or damage to neurons and axons, underlies permanent disability in multiple sclerosis (MS); yet its mechanisms are incompletely understood. Recent data indicates autoimmunity to several intraneuronal antigens, including the RNA binding protein (RBP) heterogenous nuclear ribonucleoprotein A1 (hnRNP A1), as contributors to neurodegeneration. We previously showed that addition of anti-hnRNP A1 antibodies, which target the same immunodominant domain of MS IgG, to mice with experimental autoimmune encephalomyelitis (EAE) worsened disease and resulted in an exacerbation of hnRNP A1 dysfunction including cytoplasmic mislocalization of hnRNP A1, stress granule (SG) formation and neurodegeneration in the chronic stages of disease. Because this previous study focused on a singular timepoint during EAE, it is unclear whether anti-hnRNP A1 antibody induced hnRNP A1 dysfunction caused neurodegeneration or was result of it. In the present study, we analyzed in vivo and in vitro models of anti-hnRNP A1 antibody-mediated autoimmunity for markers of hnRNP A1 dysfunction and neurodegeneration over a time course to gain a better understanding of the connection between hnRNP A1 dysfunction and neurodegeneration. Anti-hnRNP A1 antibody treatment resulted in increased neuronal hnRNP A1 mislocalization and nuclear depletion temporally followed by altered RNA expression and SG formation, and lastly an increase in necroptotic signalling and neuronal cell death. Treatment with necrostatin-1s inhibited necroptosis and partially rescued anti-hnRNP A1 antibody-mediated neurodegeneration while clathrin knockdown specifically inhibited anti-hnRNP A1 antibody uptake into neurons. This data identifies a novel antibody-mediated mechanism of neurodegeneration, which may be targeted to inhibit neurodegeneration and prevent permanent neurological decline in persons living with MS.
    MeSH term(s) Animals ; Autoimmunity ; Encephalomyelitis, Autoimmune, Experimental ; Heterogeneous Nuclear Ribonucleoprotein A1/genetics ; Heterogeneous Nuclear Ribonucleoprotein A1/metabolism ; Mice ; Multiple Sclerosis/metabolism ; Nerve Degeneration ; Neurons/metabolism ; Ribonucleoproteins
    Chemical Substances Heterogeneous Nuclear Ribonucleoprotein A1 ; Ribonucleoproteins
    Language English
    Publishing date 2022-05-23
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1211786-9
    ISSN 1095-953X ; 0969-9961
    ISSN (online) 1095-953X
    ISSN 0969-9961
    DOI 10.1016/j.nbd.2022.105775
    Database MEDical Literature Analysis and Retrieval System OnLINE

    Full text online

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.A 4444: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  6. Article ; Online: Antibodies to the RNA binding protein heterogeneous nuclear ribonucleoprotein A1 contribute to neuronal cell loss in an animal model of multiple sclerosis.

    Libner, Cole D / Salapa, Hannah E / Hutchinson, Catherine / Lee, Sangmin / Levin, Michael C

    The Journal of comparative neurology

    2020  Volume 528, Issue 10, Page(s) 1704–1724

    Abstract: Neurodegeneration, including loss of neurons and axons, is a feature of progressive forms of multiple sclerosis (MS). The mechanisms underlying neurodegeneration are mostly unknown. Research implicates autoimmunity to nonmyelin self-antigens as important ...

    Abstract Neurodegeneration, including loss of neurons and axons, is a feature of progressive forms of multiple sclerosis (MS). The mechanisms underlying neurodegeneration are mostly unknown. Research implicates autoimmunity to nonmyelin self-antigens as important contributors to disease pathogenesis. Data from our lab implicate autoimmunity to the RNA binding protein (RBP) heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) as a possible mechanism of neurodegeneration in MS. MS patients make antibodies to hnRNP A1, which have been shown to lead to neuronal dysfunction in vitro. Using an animal model of MS, experimental autoimmune encephalomyelitis (EAE), we show here that injection of anti-hnRNP A1 antibodies, in contrast to control antibodies, resulted in worsened disease and increased neurodegeneration. We found a reduction of NeuN
    MeSH term(s) Animals ; Autoantibodies/immunology ; Autoantigens/immunology ; Encephalomyelitis, Autoimmune, Experimental/immunology ; Encephalomyelitis, Autoimmune, Experimental/pathology ; Female ; Heterogeneous Nuclear Ribonucleoprotein A1/immunology ; Mice ; Mice, Inbred C57BL ; Multiple Sclerosis ; Nerve Degeneration/immunology ; Neurons/immunology ; Neurons/pathology
    Chemical Substances Autoantibodies ; Autoantigens ; Heterogeneous Nuclear Ribonucleoprotein A1
    Language English
    Publishing date 2020-01-11
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 3086-7
    ISSN 1096-9861 ; 0021-9967 ; 0092-7317
    ISSN (online) 1096-9861
    ISSN 0021-9967 ; 0092-7317
    DOI 10.1002/cne.24845
    Database MEDical Literature Analysis and Retrieval System OnLINE

    Full text online

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Ub I Zs.66: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
    ab Jg. 2022: Lesesaal (EG)

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

To top