GlutaredoxinV1, Main, Exploration, bibRecord, 000162

Glutaredoxin1 Diminishes Amyloid Beta-Mediated Oxidation of F-Actin and Reverses Cognitive Deficits in an Alzheimer's Disease Mouse Model.

Identifieur interne : 000162 ( Main/Exploration ); précédent : 000161; suivant : 000163

Glutaredoxin1 Diminishes Amyloid Beta-Mediated Oxidation of F-Actin and Reverses Cognitive Deficits in an Alzheimer's Disease Mouse Model.

Auteurs : Reddy Peera Kommaddi [Inde] ; Deepika Singh Tomar [Inde] ; Smitha Karunakaran [Inde] ; Deepti Bapat [Inde] ; Siddharth Nanguneri [Inde] ; Ajit Ray [Inde] ; Bernard L. Schneider [Suisse] ; Deepak Nair [Inde] ; Vijayalakshmi Ravindranath [Inde]

Source :

Antioxidants & redox signaling [ 1557-7716 ] ; 2019.

RBID : pubmed:31617375

Descripteurs français

English descriptors

KwdEn :
- Actins (metabolism), Alzheimer Disease (metabolism), Amyloid beta-Peptides (metabolism), Animals (MeSH), Cells, Cultured (MeSH), Cognitive Dysfunction (metabolism), Disease Models, Animal (MeSH), Glutaredoxins (analysis), Glutaredoxins (genetics), Glutaredoxins (metabolism), Male (MeSH), Mice (MeSH), Mice, Transgenic (MeSH), Oxidation-Reduction (MeSH), Presenilin-1 (metabolism), Reactive Oxygen Species (analysis), Reactive Oxygen Species (metabolism).
MESH :
- chemical , analysis : Glutaredoxins, Reactive Oxygen Species.
- chemical , genetics : Glutaredoxins.
- chemical , metabolism : Actins, Amyloid beta-Peptides, Glutaredoxins, Presenilin-1, Reactive Oxygen Species.
- metabolism : Alzheimer Disease, Cognitive Dysfunction.
- Animals, Cells, Cultured, Disease Models, Animal, Male, Mice, Mice, Transgenic, Oxidation-Reduction.

Abstract

Aims: Reactive oxygen species (ROS) generated during Alzheimer's disease (AD) pathogenesis through multiple sources are implicated in synaptic pathology observed in the disease. We have previously shown F-actin disassembly in dendritic spines in early AD (34). The actin cytoskeleton can be oxidatively modified resulting in altered F-actin dynamics. Therefore, we investigated whether disruption of redox signaling could contribute to actin network disassembly and downstream effects in the amyloid precursor protein/presenilin-1 double transgenic (APP/PS1) mouse model of AD. Results: Synaptosomal preparations from 1-month-old APP/PS1 mice showed an increase in ROS levels, coupled with a decrease in the reduced form of F-actin and increase in glutathionylated synaptosomal actin. Furthermore, synaptic glutaredoxin 1 (Grx1) and thioredoxin levels were found to be lowered. Overexpressing Grx1 in the brains of these mice not only reversed F-actin loss seen in APP/PS1 mice but also restored memory recall after contextual fear conditioning. F-actin levels and F-actin nanoarchitecture in spines were also stabilized by Grx1 overexpression in APP/PS1 primary cortical neurons, indicating that glutathionylation of F-actin is a critical event in early pathogenesis of AD, which leads to spine loss. Innovation: Loss of thiol/disulfide oxidoreductases in the synapse along with increase in ROS can render F-actin nanoarchitecture susceptible to oxidative modifications in AD. Conclusions: Our findings provide novel evidence that altered redox signaling in the form of S-glutathionylation and reduced Grx1 levels can lead to synaptic dysfunction during AD pathogenesis by directly disrupting the F-actin nanoarchitecture in spines. Increasing Grx1 levels is a potential target for novel disease-modifying therapies for AD.

DOI: 10.1089/ars.2019.7754
PubMed: 31617375

Affiliations:

Links toward previous steps (curation, corpus...)

to stream Main, to step Corpus: 000103
to stream Main, to step Curation: 000103

Le document en format XML

<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Glutaredoxin1 Diminishes Amyloid Beta-Mediated Oxidation of F-Actin and Reverses Cognitive Deficits in an Alzheimer's Disease Mouse Model.</title>
<author><name sortKey="Kommaddi, Reddy Peera" sort="Kommaddi, Reddy Peera" uniqKey="Kommaddi R" first="Reddy Peera" last="Kommaddi">Reddy Peera Kommaddi</name>
<affiliation wicri:level="1"><nlm:affiliation>Centre for Neuroscience, Indian Institute of Science, Bangalore, India.</nlm:affiliation>
<country xml:lang="fr">Inde</country>
<wicri:regionArea>Centre for Neuroscience, Indian Institute of Science, Bangalore</wicri:regionArea>
<wicri:noRegion>Bangalore</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Tomar, Deepika Singh" sort="Tomar, Deepika Singh" uniqKey="Tomar D" first="Deepika Singh" last="Tomar">Deepika Singh Tomar</name>
<affiliation wicri:level="1"><nlm:affiliation>Centre for Neuroscience, Indian Institute of Science, Bangalore, India.</nlm:affiliation>
<country xml:lang="fr">Inde</country>
<wicri:regionArea>Centre for Neuroscience, Indian Institute of Science, Bangalore</wicri:regionArea>
<wicri:noRegion>Bangalore</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Karunakaran, Smitha" sort="Karunakaran, Smitha" uniqKey="Karunakaran S" first="Smitha" last="Karunakaran">Smitha Karunakaran</name>
<affiliation wicri:level="1"><nlm:affiliation>Centre for Neuroscience, Indian Institute of Science, Bangalore, India.</nlm:affiliation>
<country xml:lang="fr">Inde</country>
<wicri:regionArea>Centre for Neuroscience, Indian Institute of Science, Bangalore</wicri:regionArea>
<wicri:noRegion>Bangalore</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Bapat, Deepti" sort="Bapat, Deepti" uniqKey="Bapat D" first="Deepti" last="Bapat">Deepti Bapat</name>
<affiliation wicri:level="1"><nlm:affiliation>Centre for Neuroscience, Indian Institute of Science, Bangalore, India.</nlm:affiliation>
<country xml:lang="fr">Inde</country>
<wicri:regionArea>Centre for Neuroscience, Indian Institute of Science, Bangalore</wicri:regionArea>
<wicri:noRegion>Bangalore</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Nanguneri, Siddharth" sort="Nanguneri, Siddharth" uniqKey="Nanguneri S" first="Siddharth" last="Nanguneri">Siddharth Nanguneri</name>
<affiliation wicri:level="1"><nlm:affiliation>Centre for Neuroscience, Indian Institute of Science, Bangalore, India.</nlm:affiliation>
<country xml:lang="fr">Inde</country>
<wicri:regionArea>Centre for Neuroscience, Indian Institute of Science, Bangalore</wicri:regionArea>
<wicri:noRegion>Bangalore</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Ray, Ajit" sort="Ray, Ajit" uniqKey="Ray A" first="Ajit" last="Ray">Ajit Ray</name>
<affiliation wicri:level="1"><nlm:affiliation>Centre for Neuroscience, Indian Institute of Science, Bangalore, India.</nlm:affiliation>
<country xml:lang="fr">Inde</country>
<wicri:regionArea>Centre for Neuroscience, Indian Institute of Science, Bangalore</wicri:regionArea>
<wicri:noRegion>Bangalore</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Schneider, Bernard L" sort="Schneider, Bernard L" uniqKey="Schneider B" first="Bernard L" last="Schneider">Bernard L. Schneider</name>
<affiliation wicri:level="3"><nlm:affiliation>Brain Mind Institute, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.</nlm:affiliation>
<country xml:lang="fr">Suisse</country>
<wicri:regionArea>Brain Mind Institute, Ecole Polytechnique Fédérale de Lausanne, Lausanne</wicri:regionArea>
<placeName><settlement type="city">Lausanne</settlement>
<region nuts="3" type="region">Canton de Vaud</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Nair, Deepak" sort="Nair, Deepak" uniqKey="Nair D" first="Deepak" last="Nair">Deepak Nair</name>
<affiliation wicri:level="1"><nlm:affiliation>Centre for Neuroscience, Indian Institute of Science, Bangalore, India.</nlm:affiliation>
<country xml:lang="fr">Inde</country>
<wicri:regionArea>Centre for Neuroscience, Indian Institute of Science, Bangalore</wicri:regionArea>
<wicri:noRegion>Bangalore</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Ravindranath, Vijayalakshmi" sort="Ravindranath, Vijayalakshmi" uniqKey="Ravindranath V" first="Vijayalakshmi" last="Ravindranath">Vijayalakshmi Ravindranath</name>
<affiliation wicri:level="1"><nlm:affiliation>Centre for Neuroscience, Indian Institute of Science, Bangalore, India.</nlm:affiliation>
<country xml:lang="fr">Inde</country>
<wicri:regionArea>Centre for Neuroscience, Indian Institute of Science, Bangalore</wicri:regionArea>
<wicri:noRegion>Bangalore</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:affiliation>Centre for Brain Research, Indian Institute of Science, Bangalore, India.</nlm:affiliation>
<country xml:lang="fr">Inde</country>
<wicri:regionArea>Centre for Brain Research, Indian Institute of Science, Bangalore</wicri:regionArea>
<wicri:noRegion>Bangalore</wicri:noRegion>
</affiliation>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">PubMed</idno>
<date when="2019">2019</date>
<idno type="RBID">pubmed:31617375</idno>
<idno type="pmid">31617375</idno>
<idno type="doi">10.1089/ars.2019.7754</idno>
<idno type="wicri:Area/Main/Corpus">000103</idno>
<idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Corpus" wicri:corpus="PubMed">000103</idno>
<idno type="wicri:Area/Main/Curation">000103</idno>
<idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Curation">000103</idno>
<idno type="wicri:Area/Main/Exploration">000103</idno>
</publicationStmt>
<sourceDesc><biblStruct><analytic><title xml:lang="en">Glutaredoxin1 Diminishes Amyloid Beta-Mediated Oxidation of F-Actin and Reverses Cognitive Deficits in an Alzheimer's Disease Mouse Model.</title>
<author><name sortKey="Kommaddi, Reddy Peera" sort="Kommaddi, Reddy Peera" uniqKey="Kommaddi R" first="Reddy Peera" last="Kommaddi">Reddy Peera Kommaddi</name>
<affiliation wicri:level="1"><nlm:affiliation>Centre for Neuroscience, Indian Institute of Science, Bangalore, India.</nlm:affiliation>
<country xml:lang="fr">Inde</country>
<wicri:regionArea>Centre for Neuroscience, Indian Institute of Science, Bangalore</wicri:regionArea>
<wicri:noRegion>Bangalore</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Tomar, Deepika Singh" sort="Tomar, Deepika Singh" uniqKey="Tomar D" first="Deepika Singh" last="Tomar">Deepika Singh Tomar</name>
<affiliation wicri:level="1"><nlm:affiliation>Centre for Neuroscience, Indian Institute of Science, Bangalore, India.</nlm:affiliation>
<country xml:lang="fr">Inde</country>
<wicri:regionArea>Centre for Neuroscience, Indian Institute of Science, Bangalore</wicri:regionArea>
<wicri:noRegion>Bangalore</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Karunakaran, Smitha" sort="Karunakaran, Smitha" uniqKey="Karunakaran S" first="Smitha" last="Karunakaran">Smitha Karunakaran</name>
<affiliation wicri:level="1"><nlm:affiliation>Centre for Neuroscience, Indian Institute of Science, Bangalore, India.</nlm:affiliation>
<country xml:lang="fr">Inde</country>
<wicri:regionArea>Centre for Neuroscience, Indian Institute of Science, Bangalore</wicri:regionArea>
<wicri:noRegion>Bangalore</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Bapat, Deepti" sort="Bapat, Deepti" uniqKey="Bapat D" first="Deepti" last="Bapat">Deepti Bapat</name>
<affiliation wicri:level="1"><nlm:affiliation>Centre for Neuroscience, Indian Institute of Science, Bangalore, India.</nlm:affiliation>
<country xml:lang="fr">Inde</country>
<wicri:regionArea>Centre for Neuroscience, Indian Institute of Science, Bangalore</wicri:regionArea>
<wicri:noRegion>Bangalore</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Nanguneri, Siddharth" sort="Nanguneri, Siddharth" uniqKey="Nanguneri S" first="Siddharth" last="Nanguneri">Siddharth Nanguneri</name>
<affiliation wicri:level="1"><nlm:affiliation>Centre for Neuroscience, Indian Institute of Science, Bangalore, India.</nlm:affiliation>
<country xml:lang="fr">Inde</country>
<wicri:regionArea>Centre for Neuroscience, Indian Institute of Science, Bangalore</wicri:regionArea>
<wicri:noRegion>Bangalore</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Ray, Ajit" sort="Ray, Ajit" uniqKey="Ray A" first="Ajit" last="Ray">Ajit Ray</name>
<affiliation wicri:level="1"><nlm:affiliation>Centre for Neuroscience, Indian Institute of Science, Bangalore, India.</nlm:affiliation>
<country xml:lang="fr">Inde</country>
<wicri:regionArea>Centre for Neuroscience, Indian Institute of Science, Bangalore</wicri:regionArea>
<wicri:noRegion>Bangalore</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Schneider, Bernard L" sort="Schneider, Bernard L" uniqKey="Schneider B" first="Bernard L" last="Schneider">Bernard L. Schneider</name>
<affiliation wicri:level="3"><nlm:affiliation>Brain Mind Institute, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.</nlm:affiliation>
<country xml:lang="fr">Suisse</country>
<wicri:regionArea>Brain Mind Institute, Ecole Polytechnique Fédérale de Lausanne, Lausanne</wicri:regionArea>
<placeName><settlement type="city">Lausanne</settlement>
<region nuts="3" type="region">Canton de Vaud</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Nair, Deepak" sort="Nair, Deepak" uniqKey="Nair D" first="Deepak" last="Nair">Deepak Nair</name>
<affiliation wicri:level="1"><nlm:affiliation>Centre for Neuroscience, Indian Institute of Science, Bangalore, India.</nlm:affiliation>
<country xml:lang="fr">Inde</country>
<wicri:regionArea>Centre for Neuroscience, Indian Institute of Science, Bangalore</wicri:regionArea>
<wicri:noRegion>Bangalore</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Ravindranath, Vijayalakshmi" sort="Ravindranath, Vijayalakshmi" uniqKey="Ravindranath V" first="Vijayalakshmi" last="Ravindranath">Vijayalakshmi Ravindranath</name>
<affiliation wicri:level="1"><nlm:affiliation>Centre for Neuroscience, Indian Institute of Science, Bangalore, India.</nlm:affiliation>
<country xml:lang="fr">Inde</country>
<wicri:regionArea>Centre for Neuroscience, Indian Institute of Science, Bangalore</wicri:regionArea>
<wicri:noRegion>Bangalore</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:affiliation>Centre for Brain Research, Indian Institute of Science, Bangalore, India.</nlm:affiliation>
<country xml:lang="fr">Inde</country>
<wicri:regionArea>Centre for Brain Research, Indian Institute of Science, Bangalore</wicri:regionArea>
<wicri:noRegion>Bangalore</wicri:noRegion>
</affiliation>
</author>
</analytic>
<series><title level="j">Antioxidants & redox signaling</title>
<idno type="eISSN">1557-7716</idno>
<imprint><date when="2019" type="published">2019</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Actins (metabolism)</term>
<term>Alzheimer Disease (metabolism)</term>
<term>Amyloid beta-Peptides (metabolism)</term>
<term>Animals (MeSH)</term>
<term>Cells, Cultured (MeSH)</term>
<term>Cognitive Dysfunction (metabolism)</term>
<term>Disease Models, Animal (MeSH)</term>
<term>Glutaredoxins (analysis)</term>
<term>Glutaredoxins (genetics)</term>
<term>Glutaredoxins (metabolism)</term>
<term>Male (MeSH)</term>
<term>Mice (MeSH)</term>
<term>Mice, Transgenic (MeSH)</term>
<term>Oxidation-Reduction (MeSH)</term>
<term>Presenilin-1 (metabolism)</term>
<term>Reactive Oxygen Species (analysis)</term>
<term>Reactive Oxygen Species (metabolism)</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>Actines (métabolisme)</term>
<term>Animaux (MeSH)</term>
<term>Cellules cultivées (MeSH)</term>
<term>Dysfonctionnement cognitif (métabolisme)</term>
<term>Espèces réactives de l'oxygène (analyse)</term>
<term>Espèces réactives de l'oxygène (métabolisme)</term>
<term>Glutarédoxines (analyse)</term>
<term>Glutarédoxines (génétique)</term>
<term>Glutarédoxines (métabolisme)</term>
<term>Maladie d'Alzheimer (métabolisme)</term>
<term>Modèles animaux de maladie humaine (MeSH)</term>
<term>Mâle (MeSH)</term>
<term>Oxydoréduction (MeSH)</term>
<term>Peptides bêta-amyloïdes (métabolisme)</term>
<term>Préséniline-1 (métabolisme)</term>
<term>Souris (MeSH)</term>
<term>Souris transgéniques (MeSH)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="analysis" xml:lang="en"><term>Glutaredoxins</term>
<term>Reactive Oxygen Species</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Glutaredoxins</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Actins</term>
<term>Amyloid beta-Peptides</term>
<term>Glutaredoxins</term>
<term>Presenilin-1</term>
<term>Reactive Oxygen Species</term>
</keywords>
<keywords scheme="MESH" qualifier="analyse" xml:lang="fr"><term>Espèces réactives de l'oxygène</term>
<term>Glutarédoxines</term>
</keywords>
<keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Glutarédoxines</term>
</keywords>
<keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Alzheimer Disease</term>
<term>Cognitive Dysfunction</term>
</keywords>
<keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Actines</term>
<term>Dysfonctionnement cognitif</term>
<term>Espèces réactives de l'oxygène</term>
<term>Glutarédoxines</term>
<term>Maladie d'Alzheimer</term>
<term>Peptides bêta-amyloïdes</term>
<term>Préséniline-1</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Animals</term>
<term>Cells, Cultured</term>
<term>Disease Models, Animal</term>
<term>Male</term>
<term>Mice</term>
<term>Mice, Transgenic</term>
<term>Oxidation-Reduction</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr"><term>Animaux</term>
<term>Cellules cultivées</term>
<term>Modèles animaux de maladie humaine</term>
<term>Mâle</term>
<term>Oxydoréduction</term>
<term>Souris</term>
<term>Souris transgéniques</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en"><b><i>Aims:</i>
</b>
 Reactive oxygen species (ROS) generated during Alzheimer's disease (AD) pathogenesis through multiple sources are implicated in synaptic pathology observed in the disease. We have previously shown F-actin disassembly in dendritic spines in early AD (34). The actin cytoskeleton can be oxidatively modified resulting in altered F-actin dynamics. Therefore, we investigated whether disruption of redox signaling could contribute to actin network disassembly and downstream effects in the amyloid precursor protein/presenilin-1 double transgenic (APP/PS1) mouse model of AD. <b><i>Results:</i>
</b>
 Synaptosomal preparations from 1-month-old APP/PS1 mice showed an increase in ROS levels, coupled with a decrease in the reduced form of F-actin and increase in glutathionylated synaptosomal actin. Furthermore, synaptic glutaredoxin 1 (Grx1) and thioredoxin levels were found to be lowered. Overexpressing Grx1 in the brains of these mice not only reversed F-actin loss seen in APP/PS1 mice but also restored memory recall after contextual fear conditioning. F-actin levels and F-actin nanoarchitecture in spines were also stabilized by Grx1 overexpression in APP/PS1 primary cortical neurons, indicating that glutathionylation of F-actin is a critical event in early pathogenesis of AD, which leads to spine loss. <b><i>Innovation:</i>
</b>
 Loss of thiol/disulfide oxidoreductases in the synapse along with increase in ROS can render F-actin nanoarchitecture susceptible to oxidative modifications in AD. <b><i>Conclusions:</i>
</b>
 Our findings provide novel evidence that altered redox signaling in the form of S-glutathionylation and reduced Grx1 levels can lead to synaptic dysfunction during AD pathogenesis by directly disrupting the F-actin nanoarchitecture in spines. Increasing Grx1 levels is a potential target for novel disease-modifying therapies for AD.</div>
</front>
</TEI>
<pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">31617375</PMID>
<DateCompleted><Year>2020</Year>
<Month>08</Month>
<Day>11</Day>
</DateCompleted>
<DateRevised><Year>2020</Year>
<Month>08</Month>
<Day>11</Day>
</DateRevised>
<Article PubModel="Print"><Journal><ISSN IssnType="Electronic">1557-7716</ISSN>
<JournalIssue CitedMedium="Internet"><Volume>31</Volume>
<Issue>18</Issue>
<PubDate><Year>2019</Year>
<Month>12</Month>
<Day>20</Day>
</PubDate>
</JournalIssue>
<Title>Antioxidants & redox signaling</Title>
<ISOAbbreviation>Antioxid Redox Signal</ISOAbbreviation>
</Journal>
<ArticleTitle>Glutaredoxin1 Diminishes Amyloid Beta-Mediated Oxidation of F-Actin and Reverses Cognitive Deficits in an Alzheimer's Disease Mouse Model.</ArticleTitle>
<Pagination><MedlinePgn>1321-1338</MedlinePgn>
</Pagination>
<ELocationID EIdType="doi" ValidYN="Y">10.1089/ars.2019.7754</ELocationID>
<Abstract><AbstractText><b><i>Aims:</i>
</b>
 Reactive oxygen species (ROS) generated during Alzheimer's disease (AD) pathogenesis through multiple sources are implicated in synaptic pathology observed in the disease. We have previously shown F-actin disassembly in dendritic spines in early AD (34). The actin cytoskeleton can be oxidatively modified resulting in altered F-actin dynamics. Therefore, we investigated whether disruption of redox signaling could contribute to actin network disassembly and downstream effects in the amyloid precursor protein/presenilin-1 double transgenic (APP/PS1) mouse model of AD. <b><i>Results:</i>
</b>
 Synaptosomal preparations from 1-month-old APP/PS1 mice showed an increase in ROS levels, coupled with a decrease in the reduced form of F-actin and increase in glutathionylated synaptosomal actin. Furthermore, synaptic glutaredoxin 1 (Grx1) and thioredoxin levels were found to be lowered. Overexpressing Grx1 in the brains of these mice not only reversed F-actin loss seen in APP/PS1 mice but also restored memory recall after contextual fear conditioning. F-actin levels and F-actin nanoarchitecture in spines were also stabilized by Grx1 overexpression in APP/PS1 primary cortical neurons, indicating that glutathionylation of F-actin is a critical event in early pathogenesis of AD, which leads to spine loss. <b><i>Innovation:</i>
</b>
 Loss of thiol/disulfide oxidoreductases in the synapse along with increase in ROS can render F-actin nanoarchitecture susceptible to oxidative modifications in AD. <b><i>Conclusions:</i>
</b>
 Our findings provide novel evidence that altered redox signaling in the form of S-glutathionylation and reduced Grx1 levels can lead to synaptic dysfunction during AD pathogenesis by directly disrupting the F-actin nanoarchitecture in spines. Increasing Grx1 levels is a potential target for novel disease-modifying therapies for AD.</AbstractText>
</Abstract>
<AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Kommaddi</LastName>
<ForeName>Reddy Peera</ForeName>
<Initials>RP</Initials>
<AffiliationInfo><Affiliation>Centre for Neuroscience, Indian Institute of Science, Bangalore, India.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Tomar</LastName>
<ForeName>Deepika Singh</ForeName>
<Initials>DS</Initials>
<AffiliationInfo><Affiliation>Centre for Neuroscience, Indian Institute of Science, Bangalore, India.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Karunakaran</LastName>
<ForeName>Smitha</ForeName>
<Initials>S</Initials>
<AffiliationInfo><Affiliation>Centre for Neuroscience, Indian Institute of Science, Bangalore, India.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Bapat</LastName>
<ForeName>Deepti</ForeName>
<Initials>D</Initials>
<AffiliationInfo><Affiliation>Centre for Neuroscience, Indian Institute of Science, Bangalore, India.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Nanguneri</LastName>
<ForeName>Siddharth</ForeName>
<Initials>S</Initials>
<AffiliationInfo><Affiliation>Centre for Neuroscience, Indian Institute of Science, Bangalore, India.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Ray</LastName>
<ForeName>Ajit</ForeName>
<Initials>A</Initials>
<AffiliationInfo><Affiliation>Centre for Neuroscience, Indian Institute of Science, Bangalore, India.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Schneider</LastName>
<ForeName>Bernard L</ForeName>
<Initials>BL</Initials>
<AffiliationInfo><Affiliation>Brain Mind Institute, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Nair</LastName>
<ForeName>Deepak</ForeName>
<Initials>D</Initials>
<AffiliationInfo><Affiliation>Centre for Neuroscience, Indian Institute of Science, Bangalore, India.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Ravindranath</LastName>
<ForeName>Vijayalakshmi</ForeName>
<Initials>V</Initials>
<AffiliationInfo><Affiliation>Centre for Neuroscience, Indian Institute of Science, Bangalore, India.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Centre for Brain Research, Indian Institute of Science, Bangalore, India.</Affiliation>
</AffiliationInfo>
</Author>
</AuthorList>
<Language>eng</Language>
<PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType>
<PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType>
</PublicationTypeList>
</Article>
<MedlineJournalInfo><Country>United States</Country>
<MedlineTA>Antioxid Redox Signal</MedlineTA>
<NlmUniqueID>100888899</NlmUniqueID>
<ISSNLinking>1523-0864</ISSNLinking>
</MedlineJournalInfo>
<ChemicalList><Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D000199">Actins</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D016229">Amyloid beta-Peptides</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="C516006">Glrx protein, mouse</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D054477">Glutaredoxins</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D053764">Presenilin-1</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D017382">Reactive Oxygen Species</NameOfSubstance>
</Chemical>
</ChemicalList>
<CitationSubset>IM</CitationSubset>
<MeshHeadingList><MeshHeading><DescriptorName UI="D000199" MajorTopicYN="N">Actins</DescriptorName>
<QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D000544" MajorTopicYN="N">Alzheimer Disease</DescriptorName>
<QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D016229" MajorTopicYN="N">Amyloid beta-Peptides</DescriptorName>
<QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D002478" MajorTopicYN="N">Cells, Cultured</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D060825" MajorTopicYN="N">Cognitive Dysfunction</DescriptorName>
<QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D004195" MajorTopicYN="Y">Disease Models, Animal</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D054477" MajorTopicYN="N">Glutaredoxins</DescriptorName>
<QualifierName UI="Q000032" MajorTopicYN="N">analysis</QualifierName>
<QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName>
<QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D008297" MajorTopicYN="N">Male</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D051379" MajorTopicYN="N">Mice</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D008822" MajorTopicYN="N">Mice, Transgenic</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D010084" MajorTopicYN="N">Oxidation-Reduction</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D053764" MajorTopicYN="N">Presenilin-1</DescriptorName>
<QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D017382" MajorTopicYN="N">Reactive Oxygen Species</DescriptorName>
<QualifierName UI="Q000032" MajorTopicYN="N">analysis</QualifierName>
<QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName>
</MeshHeading>
</MeshHeadingList>
<KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="Y">Grx1</Keyword>
<Keyword MajorTopicYN="Y">cognition</Keyword>
<Keyword MajorTopicYN="Y">cytoskeleton</Keyword>
<Keyword MajorTopicYN="Y">neurodegenerative disease</Keyword>
<Keyword MajorTopicYN="Y">oxidation</Keyword>
<Keyword MajorTopicYN="Y">reactive oxygen species</Keyword>
</KeywordList>
</MedlineCitation>
<PubmedData><History><PubMedPubDate PubStatus="pubmed"><Year>2019</Year>
<Month>10</Month>
<Day>17</Day>
<Hour>6</Hour>
<Minute>0</Minute>
</PubMedPubDate>
<PubMedPubDate PubStatus="medline"><Year>2020</Year>
<Month>8</Month>
<Day>12</Day>
<Hour>6</Hour>
<Minute>0</Minute>
</PubMedPubDate>
<PubMedPubDate PubStatus="entrez"><Year>2019</Year>
<Month>10</Month>
<Day>17</Day>
<Hour>6</Hour>
<Minute>0</Minute>
</PubMedPubDate>
</History>
<PublicationStatus>ppublish</PublicationStatus>
<ArticleIdList><ArticleId IdType="pubmed">31617375</ArticleId>
<ArticleId IdType="doi">10.1089/ars.2019.7754</ArticleId>
</ArticleIdList>
</PubmedData>
</pubmed>
<affiliations><list><country><li>Inde</li>
<li>Suisse</li>
</country>
<region><li>Canton de Vaud</li>
</region>
<settlement><li>Lausanne</li>
</settlement>
</list>
<tree><country name="Inde"><noRegion><name sortKey="Kommaddi, Reddy Peera" sort="Kommaddi, Reddy Peera" uniqKey="Kommaddi R" first="Reddy Peera" last="Kommaddi">Reddy Peera Kommaddi</name>
</noRegion>
<name sortKey="Bapat, Deepti" sort="Bapat, Deepti" uniqKey="Bapat D" first="Deepti" last="Bapat">Deepti Bapat</name>
<name sortKey="Karunakaran, Smitha" sort="Karunakaran, Smitha" uniqKey="Karunakaran S" first="Smitha" last="Karunakaran">Smitha Karunakaran</name>
<name sortKey="Nair, Deepak" sort="Nair, Deepak" uniqKey="Nair D" first="Deepak" last="Nair">Deepak Nair</name>
<name sortKey="Nanguneri, Siddharth" sort="Nanguneri, Siddharth" uniqKey="Nanguneri S" first="Siddharth" last="Nanguneri">Siddharth Nanguneri</name>
<name sortKey="Ravindranath, Vijayalakshmi" sort="Ravindranath, Vijayalakshmi" uniqKey="Ravindranath V" first="Vijayalakshmi" last="Ravindranath">Vijayalakshmi Ravindranath</name>
<name sortKey="Ravindranath, Vijayalakshmi" sort="Ravindranath, Vijayalakshmi" uniqKey="Ravindranath V" first="Vijayalakshmi" last="Ravindranath">Vijayalakshmi Ravindranath</name>
<name sortKey="Ray, Ajit" sort="Ray, Ajit" uniqKey="Ray A" first="Ajit" last="Ray">Ajit Ray</name>
<name sortKey="Tomar, Deepika Singh" sort="Tomar, Deepika Singh" uniqKey="Tomar D" first="Deepika Singh" last="Tomar">Deepika Singh Tomar</name>
</country>
<country name="Suisse"><region name="Canton de Vaud"><name sortKey="Schneider, Bernard L" sort="Schneider, Bernard L" uniqKey="Schneider B" first="Bernard L" last="Schneider">Bernard L. Schneider</name>
</region>
</country>
</tree>
</affiliations>
</record>

Pour manipuler ce document sous Unix (Dilib)

EXPLOR_STEP=$WICRI_ROOT/Bois/explor/GlutaredoxinV1/Data/Main/Exploration

HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000162 | SxmlIndent | more

HfdSelect -h $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd -nk 000162 | SxmlIndent | more

Pour mettre un lien sur cette page dans le réseau Wicri

{{Explor lien
   |wiki=    Bois
   |area=    GlutaredoxinV1
   |flux=    Main
   |étape=   Exploration
   |type=    RBID
   |clé=     pubmed:31617375
   |texte=   Glutaredoxin1 Diminishes Amyloid Beta-Mediated Oxidation of F-Actin and Reverses Cognitive Deficits in an Alzheimer's Disease Mouse Model.
}}

Pour générer des pages wiki

HfdIndexSelect -h $EXPLOR_AREA/Data/Main/Exploration/RBID.i   -Sk "pubmed:31617375" \
       | HfdSelect -Kh $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd   \
       | NlmPubMed2Wicri -a GlutaredoxinV1

This area was generated with Dilib version V0.6.37.
Data generation: Wed Nov 18 15:13:42 2020. Site generation: Wed Nov 18 15:16:12 2020

	Serveur d'exploration sur la glutarédoxine
	Attention, ce site est en cours de développement ! Attention, site généré par des moyens informatiques à partir de corpus bruts. Les informations ne sont donc pas validées.

Serveur d'exploration sur la glutarédoxine

Glutaredoxin1 Diminishes Amyloid Beta-Mediated Oxidation of F-Actin and Reverses Cognitive Deficits in an Alzheimer's Disease Mouse Model.

Glutaredoxin1 Diminishes Amyloid Beta-Mediated Oxidation of F-Actin and Reverses Cognitive Deficits in an Alzheimer's Disease Mouse Model.

Source :

Descripteurs français

English descriptors

Abstract

Links toward previous steps (curation, corpus...)

Le document en format XML

Pour manipuler ce document sous Unix (Dilib)

Pour mettre un lien sur cette page dans le réseau Wicri

Pour générer des pages wiki