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We are analyzing https://link.springer.com/article/10.1007/s13311-021-01130-6.

Title:
MicroRNA-7 Protects Against Neurodegeneration Induced by α-Synuclein Preformed Fibrils in the Mouse Brain | Neurotherapeutics
Description:
α-Synuclein is a key protein in the pathogenesis of Parkinson’s disease as it accumulates in fibrillar form in affected brain regions. Misfolded α-synuclein seeds recruit monomeric α-synuclein to form aggregates, which can spread to anatomically connected brain regions, a phenomenon that correlates with clinical disease progression. Thus, downregulating α-synuclein levels could reduce seeding and inhibit aggregate formation and propagation. We previously reported that microRNA-7 (miR-7) protects neuronal cells by downregulating α-synuclein expression through its effect on the 3′-untranslated region of SNCA mRNA; however, whether miR-7 blocks α-synuclein seeding and propagation in vivo remains unknown. Here, we induced miR-7 overexpression in the mouse striatum unilaterally by infusing adeno-associated virus 1 (AAV-miR-7) followed by inoculation with recombinant α-synuclein preformed fibrils (PFF) a month later. Compared with control mice injected with non-targeting AAV-miR-NT followed by PFF, AAV-miR-7 pre-injected mice exhibited lower levels of monomeric and high-molecular-weight α-synuclein species in the striatum, and reduced amount of phosphorylated α-synuclein in the striatum and in nigral dopamine neurons. Accordingly, AAV-miR-7-injected mice had less pronounced degeneration of the nigrostriatal pathway and better behavioral performance. The neuroinflammatory reaction to α-synuclein PFF inoculation was also significantly attenuated. These data suggest that miR-7 inhibits the formation and propagation of pathological α-synuclein and protects against neurodegeneration induced by PFF. Collectively, these findings support the potential of miR-7 as a disease modifying biologic agent for Parkinson’s disease and related α-synucleinopathies.
Website Age:
28 years and 1 months (reg. 1997-05-29).

Matching Content Categories {📚}

  • Education
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Content Management System {📝}

What CMS is link.springer.com built with?

Custom-built

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🌠 Phenomenal Traffic: 5M - 10M visitors per month


Based on our best estimate, this website will receive around 5,000,019 visitors per month in the current month.
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How Does Link.springer.com Make Money? {💸}

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Keywords {🔍}

αsyn, pubmed, article, google, scholar, pff, mice, cas, neurons, disease, aavmir, αsynuclein, striatum, parkinsons, alphasynuclein, mouse, fig, central, dopaminergic, cells, protein, data, aggregates, levels, brain, expression, sections, cell, injection, analysis, microrna, zhang, preinjected, model, propagation, inoculation, aavmirnt, protects, neurodegeneration, neuronal, vivo, overexpression, snpc, study, aav, pbs, striatal, staining, ipsilateral, formation,

Topics {✒️}

nitro-blue-toluidine/5-bromo-4-chloro-3-indolyl-phosphate control aav-mir-nt pre-injected abundant ps129-α-syn-labeled cells ps129-α-syn-positive cell counts aav-mir-nt pre-injected mice high-molecular-weight α-synuclein species aav-mir-7 pre-injected + pff mice targeting aav-mir-nt-injected mice ps129-α-syn-immunoreactive inclusions aav1-ef1α-ctl-mir-egfp aav-mir-nt pre-injected ]fluoro-l-m-tyrosine imaging form ps129-α-syn-positive aggregates aav-mir-nt-infused brain sections abundant ps129-α-syn immunoreactivity ps129-α-syn immunoreactive neurons aav-mir-7 pre-injected mice α-syn pff-inoculated side ps129-α-syn-positive cells 1-methyl-4-phenylpyridinium-induced cell death control aav-nt-injected brains aav-mediated α-syn overexpression α-syn pff-inoculated mice alpha-synuclein-induced microglial activation α-synuclein preformed fibrils recruit endogenous α-syn aav-mir-7 pre-injection resulted α-syn pff-inoculated brains sh-sy5y cells lowering α-syn production reducing α-syn levels downregulating α-synuclein levels α-syn pff-inoculated groups intrastriatal alpha-synuclein fibrils regulate α-syn levels aav-mir-7 pre-injected downregulating α-syn levels long-term rnai knockdown pathological α-synuclein initiates anti-α-synuclein aso delivered repressing α-syn levels sonicated α-syn fibrils a53t-aav synuclein rats native α-synuclein protein aav-injected mice showed downregulating α-synuclein expression monomeric α-syn protein including lenti-mir-nt α-syn pff inoculations α-synuclein pff inoculation

Schema {🗺️}

WebPage:
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         headline:MicroRNA-7 Protects Against Neurodegeneration Induced by α-Synuclein Preformed Fibrils in the Mouse Brain
         description:α-Synuclein is a key protein in the pathogenesis of Parkinson’s disease as it accumulates in fibrillar form in affected brain regions. Misfolded α-synuclein seeds recruit monomeric α-synuclein to form aggregates, which can spread to anatomically connected brain regions, a phenomenon that correlates with clinical disease progression. Thus, downregulating α-synuclein levels could reduce seeding and inhibit aggregate formation and propagation. We previously reported that microRNA-7 (miR-7) protects neuronal cells by downregulating α-synuclein expression through its effect on the 3′-untranslated region of SNCA mRNA; however, whether miR-7 blocks α-synuclein seeding and propagation in vivo remains unknown. Here, we induced miR-7 overexpression in the mouse striatum unilaterally by infusing adeno-associated virus 1 (AAV-miR-7) followed by inoculation with recombinant α-synuclein preformed fibrils (PFF) a month later. Compared with control mice injected with non-targeting AAV-miR-NT followed by PFF, AAV-miR-7 pre-injected mice exhibited lower levels of monomeric and high-molecular-weight α-synuclein species in the striatum, and reduced amount of phosphorylated α-synuclein in the striatum and in nigral dopamine neurons. Accordingly, AAV-miR-7-injected mice had less pronounced degeneration of the nigrostriatal pathway and better behavioral performance. The neuroinflammatory reaction to α-synuclein PFF inoculation was also significantly attenuated. These data suggest that miR-7 inhibits the formation and propagation of pathological α-synuclein and protects against neurodegeneration induced by PFF. Collectively, these findings support the potential of miR-7 as a disease modifying biologic agent for Parkinson’s disease and related α-synucleinopathies.
         datePublished:2021-10-25T00:00:00Z
         dateModified:2021-10-25T00:00:00Z
         pageStart:2529
         pageEnd:2540
         sameAs:https://doi.org/10.1007/s13311-021-01130-6
         keywords:
            Parkinson’s disease
            α-Synucleinopathies
            α-Synuclein
            Pre-formed fibrils
            microRNA-7
            Neurosciences
            Neurology
            Neurosurgery
            Neurobiology
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                        name:Current address: Sanyou Biopharmaceuticals Co., Ltd., Shanghai, China
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                     name:Rutgers - Robert Wood Johnson Medical School
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                        type:PostalAddress
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               name:Santhosh Maddila
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                        name:RWJMS Institute for Neurological Therapeutics and Department of Neurology, Rutgers - Robert Wood Johnson Medical School, Piscataway, USA
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                        name:RWJMS Institute for Neurological Therapeutics and Department of Neurology, Rutgers - Robert Wood Johnson Medical School, Piscataway, USA
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                     name:Rutgers - Robert Wood Johnson Medical School
                     address:
                        name:RWJMS Institute for Neurological Therapeutics and Department of Neurology, Rutgers - Robert Wood Johnson Medical School, Piscataway, USA
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      headline:MicroRNA-7 Protects Against Neurodegeneration Induced by α-Synuclein Preformed Fibrils in the Mouse Brain
      description:α-Synuclein is a key protein in the pathogenesis of Parkinson’s disease as it accumulates in fibrillar form in affected brain regions. Misfolded α-synuclein seeds recruit monomeric α-synuclein to form aggregates, which can spread to anatomically connected brain regions, a phenomenon that correlates with clinical disease progression. Thus, downregulating α-synuclein levels could reduce seeding and inhibit aggregate formation and propagation. We previously reported that microRNA-7 (miR-7) protects neuronal cells by downregulating α-synuclein expression through its effect on the 3′-untranslated region of SNCA mRNA; however, whether miR-7 blocks α-synuclein seeding and propagation in vivo remains unknown. Here, we induced miR-7 overexpression in the mouse striatum unilaterally by infusing adeno-associated virus 1 (AAV-miR-7) followed by inoculation with recombinant α-synuclein preformed fibrils (PFF) a month later. Compared with control mice injected with non-targeting AAV-miR-NT followed by PFF, AAV-miR-7 pre-injected mice exhibited lower levels of monomeric and high-molecular-weight α-synuclein species in the striatum, and reduced amount of phosphorylated α-synuclein in the striatum and in nigral dopamine neurons. Accordingly, AAV-miR-7-injected mice had less pronounced degeneration of the nigrostriatal pathway and better behavioral performance. The neuroinflammatory reaction to α-synuclein PFF inoculation was also significantly attenuated. These data suggest that miR-7 inhibits the formation and propagation of pathological α-synuclein and protects against neurodegeneration induced by PFF. Collectively, these findings support the potential of miR-7 as a disease modifying biologic agent for Parkinson’s disease and related α-synucleinopathies.
      datePublished:2021-10-25T00:00:00Z
      dateModified:2021-10-25T00:00:00Z
      pageStart:2529
      pageEnd:2540
      sameAs:https://doi.org/10.1007/s13311-021-01130-6
      keywords:
         Parkinson’s disease
         α-Synucleinopathies
         α-Synuclein
         Pre-formed fibrils
         microRNA-7
         Neurosciences
         Neurology
         Neurosurgery
         Neurobiology
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            Periodical
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      publisher:
         name:Springer International Publishing
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            url:https://www.springernature.com/app-sn/public/images/logo-springernature.png
            type:ImageObject
         type:Organization
      author:
            name:Jie Zhang
            affiliation:
                  name:Rutgers - Robert Wood Johnson Medical School
                  address:
                     name:RWJMS Institute for Neurological Therapeutics and Department of Neurology, Rutgers - Robert Wood Johnson Medical School, Piscataway, USA
                     type:PostalAddress
                  type:Organization
            type:Person
            name:Mengyuan Zhao
            affiliation:
                  name:Rutgers - Robert Wood Johnson Medical School
                  address:
                     name:RWJMS Institute for Neurological Therapeutics and Department of Neurology, Rutgers - Robert Wood Johnson Medical School, Piscataway, USA
                     type:PostalAddress
                  type:Organization
            type:Person
            name:Run Yan
            affiliation:
                  name:Rutgers - Robert Wood Johnson Medical School
                  address:
                     name:RWJMS Institute for Neurological Therapeutics and Department of Neurology, Rutgers - Robert Wood Johnson Medical School, Piscataway, USA
                     type:PostalAddress
                  type:Organization
                  name:Current address: Sanyou Biopharmaceuticals Co., Ltd.
                  address:
                     name:Current address: Sanyou Biopharmaceuticals Co., Ltd., Shanghai, China
                     type:PostalAddress
                  type:Organization
            type:Person
            name:Jun Liu
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                  name:Rutgers - Robert Wood Johnson Medical School
                  address:
                     name:RWJMS Institute for Neurological Therapeutics and Department of Neurology, Rutgers - Robert Wood Johnson Medical School, Piscataway, USA
                     type:PostalAddress
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            type:Person
            name:Santhosh Maddila
            affiliation:
                  name:Rutgers - Robert Wood Johnson Medical School
                  address:
                     name:RWJMS Institute for Neurological Therapeutics and Department of Neurology, Rutgers - Robert Wood Johnson Medical School, Piscataway, USA
                     type:PostalAddress
                  type:Organization
            type:Person
            name:Eunsung Junn
            affiliation:
                  name:Rutgers - Robert Wood Johnson Medical School
                  address:
                     name:RWJMS Institute for Neurological Therapeutics and Department of Neurology, Rutgers - Robert Wood Johnson Medical School, Piscataway, USA
                     type:PostalAddress
                  type:Organization
            type:Person
            name:M. Maral Mouradian
            url:http://orcid.org/0000-0002-9937-412X
            affiliation:
                  name:Rutgers - Robert Wood Johnson Medical School
                  address:
                     name:RWJMS Institute for Neurological Therapeutics and Department of Neurology, Rutgers - Robert Wood Johnson Medical School, Piscataway, USA
                     type:PostalAddress
                  type:Organization
            email:[email protected]
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      name:Neurotherapeutics
      issn:
         1878-7479
         1933-7213
      volumeNumber:18
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      name:Springer International Publishing
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         url:https://www.springernature.com/app-sn/public/images/logo-springernature.png
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      name:Rutgers - Robert Wood Johnson Medical School
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      name:Rutgers - Robert Wood Johnson Medical School
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         name:RWJMS Institute for Neurological Therapeutics and Department of Neurology, Rutgers - Robert Wood Johnson Medical School, Piscataway, USA
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      name:Rutgers - Robert Wood Johnson Medical School
      address:
         name:RWJMS Institute for Neurological Therapeutics and Department of Neurology, Rutgers - Robert Wood Johnson Medical School, Piscataway, USA
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         name:Current address: Sanyou Biopharmaceuticals Co., Ltd., Shanghai, China
         type:PostalAddress
      name:Rutgers - Robert Wood Johnson Medical School
      address:
         name:RWJMS Institute for Neurological Therapeutics and Department of Neurology, Rutgers - Robert Wood Johnson Medical School, Piscataway, USA
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      name:Rutgers - Robert Wood Johnson Medical School
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         name:RWJMS Institute for Neurological Therapeutics and Department of Neurology, Rutgers - Robert Wood Johnson Medical School, Piscataway, USA
         type:PostalAddress
      name:Rutgers - Robert Wood Johnson Medical School
      address:
         name:RWJMS Institute for Neurological Therapeutics and Department of Neurology, Rutgers - Robert Wood Johnson Medical School, Piscataway, USA
         type:PostalAddress
      name:Rutgers - Robert Wood Johnson Medical School
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         type:PostalAddress
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Person:
      name:Jie Zhang
      affiliation:
            name:Rutgers - Robert Wood Johnson Medical School
            address:
               name:RWJMS Institute for Neurological Therapeutics and Department of Neurology, Rutgers - Robert Wood Johnson Medical School, Piscataway, USA
               type:PostalAddress
            type:Organization
      name:Mengyuan Zhao
      affiliation:
            name:Rutgers - Robert Wood Johnson Medical School
            address:
               name:RWJMS Institute for Neurological Therapeutics and Department of Neurology, Rutgers - Robert Wood Johnson Medical School, Piscataway, USA
               type:PostalAddress
            type:Organization
      name:Run Yan
      affiliation:
            name:Rutgers - Robert Wood Johnson Medical School
            address:
               name:RWJMS Institute for Neurological Therapeutics and Department of Neurology, Rutgers - Robert Wood Johnson Medical School, Piscataway, USA
               type:PostalAddress
            type:Organization
            name:Current address: Sanyou Biopharmaceuticals Co., Ltd.
            address:
               name:Current address: Sanyou Biopharmaceuticals Co., Ltd., Shanghai, China
               type:PostalAddress
            type:Organization
      name:Jun Liu
      affiliation:
            name:Rutgers - Robert Wood Johnson Medical School
            address:
               name:RWJMS Institute for Neurological Therapeutics and Department of Neurology, Rutgers - Robert Wood Johnson Medical School, Piscataway, USA
               type:PostalAddress
            type:Organization
      name:Santhosh Maddila
      affiliation:
            name:Rutgers - Robert Wood Johnson Medical School
            address:
               name:RWJMS Institute for Neurological Therapeutics and Department of Neurology, Rutgers - Robert Wood Johnson Medical School, Piscataway, USA
               type:PostalAddress
            type:Organization
      name:Eunsung Junn
      affiliation:
            name:Rutgers - Robert Wood Johnson Medical School
            address:
               name:RWJMS Institute for Neurological Therapeutics and Department of Neurology, Rutgers - Robert Wood Johnson Medical School, Piscataway, USA
               type:PostalAddress
            type:Organization
      name:M. Maral Mouradian
      url:http://orcid.org/0000-0002-9937-412X
      affiliation:
            name:Rutgers - Robert Wood Johnson Medical School
            address:
               name:RWJMS Institute for Neurological Therapeutics and Department of Neurology, Rutgers - Robert Wood Johnson Medical School, Piscataway, USA
               type:PostalAddress
            type:Organization
      email:[email protected]
PostalAddress:
      name:RWJMS Institute for Neurological Therapeutics and Department of Neurology, Rutgers - Robert Wood Johnson Medical School, Piscataway, USA
      name:RWJMS Institute for Neurological Therapeutics and Department of Neurology, Rutgers - Robert Wood Johnson Medical School, Piscataway, USA
      name:RWJMS Institute for Neurological Therapeutics and Department of Neurology, Rutgers - Robert Wood Johnson Medical School, Piscataway, USA
      name:Current address: Sanyou Biopharmaceuticals Co., Ltd., Shanghai, China
      name:RWJMS Institute for Neurological Therapeutics and Department of Neurology, Rutgers - Robert Wood Johnson Medical School, Piscataway, USA
      name:RWJMS Institute for Neurological Therapeutics and Department of Neurology, Rutgers - Robert Wood Johnson Medical School, Piscataway, USA
      name:RWJMS Institute for Neurological Therapeutics and Department of Neurology, Rutgers - Robert Wood Johnson Medical School, Piscataway, USA
      name:RWJMS Institute for Neurological Therapeutics and Department of Neurology, Rutgers - Robert Wood Johnson Medical School, Piscataway, USA

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