Lysosomes and α-synuclein form a dangerous duet leading to neuronal cell death.
Identifieur interne : 000648 ( Hal/Corpus ); précédent : 000647; suivant : 000649Lysosomes and α-synuclein form a dangerous duet leading to neuronal cell death.
Auteurs : Mathieu Bourdenx ; Erwan Bezard ; Benjamin DehaySource :
- Frontiers in Neuroanatomy [ 1662-5129 ] ; 2014-08-14.
Abstract
Neurodegenerative diseases are (i) characterized by a selective neuronal vulnerability to degeneration in specific brain regions; and (ii) likely to be caused by disease-specific protein misfolding. Parkinson's disease (PD) is characterized by the presence of intraneuronal proteinacious cytoplasmic inclusions, called Lewy Bodies (LB). α-Synuclein, an aggregation prone protein, has been identified as a major protein component of LB and the causative for autosomal dominant PD. Lysosomes are responsible for the clearance of long-lived proteins, such as α-synuclein, and for the removal of old or damaged organelles, such as mitochondria. Interestingly, PD-linked α-synuclein mutants and dopamine-modified wild-type α-synuclein block its own degradation, which result in insufficient clearance, leading to its aggregation and cell toxicity. Moreover, both lysosomes and lysosomal proteases have been found to be involved in the activation of certain cell death pathways. Interestingly, lysosomal alterations are observed in the brains of patients suffering from sporadic PD and also in toxic and genetic rodent models of PD-related neurodegeneration. All these events have unraveled a causal link between lysosomal impairment, α-synuclein accumulation, and neurotoxicity. In this review, we emphasize the pathophysiological mechanisms connecting α-synuclein and lysosomal dysfunction in neuronal cell death.
Url:
DOI: 10.3389
Links to Exploration step
Hal:hal-01215533Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Lysosomes and α-synuclein form a dangerous duet leading to neuronal cell death.</title>
<author><name sortKey="Bourdenx, Mathieu" sort="Bourdenx, Mathieu" uniqKey="Bourdenx M" first="Mathieu" last="Bourdenx">Mathieu Bourdenx</name>
<affiliation><hal:affiliation type="laboratory" xml:id="struct-244085" status="VALID"> <orgName>Institut des Maladies Neurodégénératives [Bordeaux]</orgName>
<orgName type="acronym">IMN</orgName>
<desc> <address> <addrLine>Bât. 3b 1er étage 146 Rue Léo Saignat 33076 Bordeaux </addrLine>
<country key="FR"></country>
</address>
<ref type="url">http://imn-bordeaux.org/</ref>
</desc>
<listRelation> <relation active="#struct-259761" type="direct"></relation>
<relation name="UMR5293" active="#struct-441569" type="direct"></relation>
</listRelation>
<tutelles><tutelle active="#struct-259761" type="direct"><org type="institution" xml:id="struct-259761" status="VALID"> <orgName>Université de Bordeaux</orgName>
<orgName type="acronym">UB</orgName>
<desc> <address> <addrLine>35, place Pey Berland - 33076 Bordeaux</addrLine>
<country key="FR"></country>
</address>
<ref type="url">http://www.u-bordeaux.fr/</ref>
</desc>
</org>
</tutelle>
<tutelle name="UMR5293" active="#struct-441569" type="direct"><org type="institution" xml:id="struct-441569" status="VALID"> <idno type="IdRef">02636817X</idno>
<idno type="ISNI">0000000122597504</idno>
<orgName>Centre National de la Recherche Scientifique</orgName>
<orgName type="acronym">CNRS</orgName>
<date type="start">1939-10-19</date>
<desc> <address> <country key="FR"></country>
</address>
<ref type="url">http://www.cnrs.fr/</ref>
</desc>
</org>
</tutelle>
</tutelles>
</hal:affiliation>
</affiliation>
</author>
<author><name sortKey="Bezard, Erwan" sort="Bezard, Erwan" uniqKey="Bezard E" first="Erwan" last="Bezard">Erwan Bezard</name>
<affiliation><hal:affiliation type="laboratory" xml:id="struct-244085" status="VALID"> <orgName>Institut des Maladies Neurodégénératives [Bordeaux]</orgName>
<orgName type="acronym">IMN</orgName>
<desc> <address> <addrLine>Bât. 3b 1er étage 146 Rue Léo Saignat 33076 Bordeaux </addrLine>
<country key="FR"></country>
</address>
<ref type="url">http://imn-bordeaux.org/</ref>
</desc>
<listRelation> <relation active="#struct-259761" type="direct"></relation>
<relation name="UMR5293" active="#struct-441569" type="direct"></relation>
</listRelation>
<tutelles><tutelle active="#struct-259761" type="direct"><org type="institution" xml:id="struct-259761" status="VALID"> <orgName>Université de Bordeaux</orgName>
<orgName type="acronym">UB</orgName>
<desc> <address> <addrLine>35, place Pey Berland - 33076 Bordeaux</addrLine>
<country key="FR"></country>
</address>
<ref type="url">http://www.u-bordeaux.fr/</ref>
</desc>
</org>
</tutelle>
<tutelle name="UMR5293" active="#struct-441569" type="direct"><org type="institution" xml:id="struct-441569" status="VALID"> <idno type="IdRef">02636817X</idno>
<idno type="ISNI">0000000122597504</idno>
<orgName>Centre National de la Recherche Scientifique</orgName>
<orgName type="acronym">CNRS</orgName>
<date type="start">1939-10-19</date>
<desc> <address> <country key="FR"></country>
</address>
<ref type="url">http://www.cnrs.fr/</ref>
</desc>
</org>
</tutelle>
</tutelles>
</hal:affiliation>
</affiliation>
</author>
<author><name sortKey="Dehay, Benjamin" sort="Dehay, Benjamin" uniqKey="Dehay B" first="Benjamin" last="Dehay">Benjamin Dehay</name>
<affiliation><hal:affiliation type="laboratory" xml:id="struct-244085" status="VALID"> <orgName>Institut des Maladies Neurodégénératives [Bordeaux]</orgName>
<orgName type="acronym">IMN</orgName>
<desc> <address> <addrLine>Bât. 3b 1er étage 146 Rue Léo Saignat 33076 Bordeaux </addrLine>
<country key="FR"></country>
</address>
<ref type="url">http://imn-bordeaux.org/</ref>
</desc>
<listRelation> <relation active="#struct-259761" type="direct"></relation>
<relation name="UMR5293" active="#struct-441569" type="direct"></relation>
</listRelation>
<tutelles><tutelle active="#struct-259761" type="direct"><org type="institution" xml:id="struct-259761" status="VALID"> <orgName>Université de Bordeaux</orgName>
<orgName type="acronym">UB</orgName>
<desc> <address> <addrLine>35, place Pey Berland - 33076 Bordeaux</addrLine>
<country key="FR"></country>
</address>
<ref type="url">http://www.u-bordeaux.fr/</ref>
</desc>
</org>
</tutelle>
<tutelle name="UMR5293" active="#struct-441569" type="direct"><org type="institution" xml:id="struct-441569" status="VALID"> <idno type="IdRef">02636817X</idno>
<idno type="ISNI">0000000122597504</idno>
<orgName>Centre National de la Recherche Scientifique</orgName>
<orgName type="acronym">CNRS</orgName>
<date type="start">1939-10-19</date>
<desc> <address> <country key="FR"></country>
</address>
<ref type="url">http://www.cnrs.fr/</ref>
</desc>
</org>
</tutelle>
</tutelles>
</hal:affiliation>
</affiliation>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">HAL</idno>
<idno type="RBID">Hal:hal-01215533</idno>
<idno type="halId">hal-01215533</idno>
<idno type="halUri">https://hal.archives-ouvertes.fr/hal-01215533</idno>
<idno type="url">https://hal.archives-ouvertes.fr/hal-01215533</idno>
<idno type="doi">10.3389</idno>
<date when="2014-08-14">2014-08-14</date>
<idno type="wicri:Area/Hal/Corpus">000648</idno>
</publicationStmt>
<sourceDesc><biblStruct><analytic><title xml:lang="en">Lysosomes and α-synuclein form a dangerous duet leading to neuronal cell death.</title>
<author><name sortKey="Bourdenx, Mathieu" sort="Bourdenx, Mathieu" uniqKey="Bourdenx M" first="Mathieu" last="Bourdenx">Mathieu Bourdenx</name>
<affiliation><hal:affiliation type="laboratory" xml:id="struct-244085" status="VALID"> <orgName>Institut des Maladies Neurodégénératives [Bordeaux]</orgName>
<orgName type="acronym">IMN</orgName>
<desc> <address> <addrLine>Bât. 3b 1er étage 146 Rue Léo Saignat 33076 Bordeaux </addrLine>
<country key="FR"></country>
</address>
<ref type="url">http://imn-bordeaux.org/</ref>
</desc>
<listRelation> <relation active="#struct-259761" type="direct"></relation>
<relation name="UMR5293" active="#struct-441569" type="direct"></relation>
</listRelation>
<tutelles><tutelle active="#struct-259761" type="direct"><org type="institution" xml:id="struct-259761" status="VALID"> <orgName>Université de Bordeaux</orgName>
<orgName type="acronym">UB</orgName>
<desc> <address> <addrLine>35, place Pey Berland - 33076 Bordeaux</addrLine>
<country key="FR"></country>
</address>
<ref type="url">http://www.u-bordeaux.fr/</ref>
</desc>
</org>
</tutelle>
<tutelle name="UMR5293" active="#struct-441569" type="direct"><org type="institution" xml:id="struct-441569" status="VALID"> <idno type="IdRef">02636817X</idno>
<idno type="ISNI">0000000122597504</idno>
<orgName>Centre National de la Recherche Scientifique</orgName>
<orgName type="acronym">CNRS</orgName>
<date type="start">1939-10-19</date>
<desc> <address> <country key="FR"></country>
</address>
<ref type="url">http://www.cnrs.fr/</ref>
</desc>
</org>
</tutelle>
</tutelles>
</hal:affiliation>
</affiliation>
</author>
<author><name sortKey="Bezard, Erwan" sort="Bezard, Erwan" uniqKey="Bezard E" first="Erwan" last="Bezard">Erwan Bezard</name>
<affiliation><hal:affiliation type="laboratory" xml:id="struct-244085" status="VALID"> <orgName>Institut des Maladies Neurodégénératives [Bordeaux]</orgName>
<orgName type="acronym">IMN</orgName>
<desc> <address> <addrLine>Bât. 3b 1er étage 146 Rue Léo Saignat 33076 Bordeaux </addrLine>
<country key="FR"></country>
</address>
<ref type="url">http://imn-bordeaux.org/</ref>
</desc>
<listRelation> <relation active="#struct-259761" type="direct"></relation>
<relation name="UMR5293" active="#struct-441569" type="direct"></relation>
</listRelation>
<tutelles><tutelle active="#struct-259761" type="direct"><org type="institution" xml:id="struct-259761" status="VALID"> <orgName>Université de Bordeaux</orgName>
<orgName type="acronym">UB</orgName>
<desc> <address> <addrLine>35, place Pey Berland - 33076 Bordeaux</addrLine>
<country key="FR"></country>
</address>
<ref type="url">http://www.u-bordeaux.fr/</ref>
</desc>
</org>
</tutelle>
<tutelle name="UMR5293" active="#struct-441569" type="direct"><org type="institution" xml:id="struct-441569" status="VALID"> <idno type="IdRef">02636817X</idno>
<idno type="ISNI">0000000122597504</idno>
<orgName>Centre National de la Recherche Scientifique</orgName>
<orgName type="acronym">CNRS</orgName>
<date type="start">1939-10-19</date>
<desc> <address> <country key="FR"></country>
</address>
<ref type="url">http://www.cnrs.fr/</ref>
</desc>
</org>
</tutelle>
</tutelles>
</hal:affiliation>
</affiliation>
</author>
<author><name sortKey="Dehay, Benjamin" sort="Dehay, Benjamin" uniqKey="Dehay B" first="Benjamin" last="Dehay">Benjamin Dehay</name>
<affiliation><hal:affiliation type="laboratory" xml:id="struct-244085" status="VALID"> <orgName>Institut des Maladies Neurodégénératives [Bordeaux]</orgName>
<orgName type="acronym">IMN</orgName>
<desc> <address> <addrLine>Bât. 3b 1er étage 146 Rue Léo Saignat 33076 Bordeaux </addrLine>
<country key="FR"></country>
</address>
<ref type="url">http://imn-bordeaux.org/</ref>
</desc>
<listRelation> <relation active="#struct-259761" type="direct"></relation>
<relation name="UMR5293" active="#struct-441569" type="direct"></relation>
</listRelation>
<tutelles><tutelle active="#struct-259761" type="direct"><org type="institution" xml:id="struct-259761" status="VALID"> <orgName>Université de Bordeaux</orgName>
<orgName type="acronym">UB</orgName>
<desc> <address> <addrLine>35, place Pey Berland - 33076 Bordeaux</addrLine>
<country key="FR"></country>
</address>
<ref type="url">http://www.u-bordeaux.fr/</ref>
</desc>
</org>
</tutelle>
<tutelle name="UMR5293" active="#struct-441569" type="direct"><org type="institution" xml:id="struct-441569" status="VALID"> <idno type="IdRef">02636817X</idno>
<idno type="ISNI">0000000122597504</idno>
<orgName>Centre National de la Recherche Scientifique</orgName>
<orgName type="acronym">CNRS</orgName>
<date type="start">1939-10-19</date>
<desc> <address> <country key="FR"></country>
</address>
<ref type="url">http://www.cnrs.fr/</ref>
</desc>
</org>
</tutelle>
</tutelles>
</hal:affiliation>
</affiliation>
</author>
</analytic>
<idno type="DOI">10.3389</idno>
<series><title level="j">Frontiers in Neuroanatomy</title>
<idno type="ISSN">1662-5129</idno>
<imprint><date type="datePub">2014-08-14</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass></textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en">Neurodegenerative diseases are (i) characterized by a selective neuronal vulnerability to degeneration in specific brain regions; and (ii) likely to be caused by disease-specific protein misfolding. Parkinson's disease (PD) is characterized by the presence of intraneuronal proteinacious cytoplasmic inclusions, called Lewy Bodies (LB). α-Synuclein, an aggregation prone protein, has been identified as a major protein component of LB and the causative for autosomal dominant PD. Lysosomes are responsible for the clearance of long-lived proteins, such as α-synuclein, and for the removal of old or damaged organelles, such as mitochondria. Interestingly, PD-linked α-synuclein mutants and dopamine-modified wild-type α-synuclein block its own degradation, which result in insufficient clearance, leading to its aggregation and cell toxicity. Moreover, both lysosomes and lysosomal proteases have been found to be involved in the activation of certain cell death pathways. Interestingly, lysosomal alterations are observed in the brains of patients suffering from sporadic PD and also in toxic and genetic rodent models of PD-related neurodegeneration. All these events have unraveled a causal link between lysosomal impairment, α-synuclein accumulation, and neurotoxicity. In this review, we emphasize the pathophysiological mechanisms connecting α-synuclein and lysosomal dysfunction in neuronal cell death.</div>
</front>
</TEI>
<hal api="V3"> <titleStmt> <title xml:lang="en">Lysosomes and α-synuclein form a dangerous duet leading to neuronal cell death.</title>
<author role="aut"> <persName> <forename type="first">Mathieu</forename>
<surname>Bourdenx</surname>
</persName>
<idno type="halauthorid">1059960</idno>
<affiliation ref="#struct-244085"></affiliation>
</author>
<author role="aut"> <persName> <forename type="first">Erwan</forename>
<surname>Bezard</surname>
</persName>
<idno type="halauthorid">537314</idno>
<affiliation ref="#struct-244085"></affiliation>
</author>
<author role="aut"> <persName> <forename type="first">Benjamin</forename>
<surname>Dehay</surname>
</persName>
<idno type="halauthorid">159357</idno>
<affiliation ref="#struct-244085"></affiliation>
</author>
<editor role="depositor"> <persName> <forename>Chantal</forename>
<surname>GUERIN</surname>
</persName>
<email type="md5">eb4bde61f74652335183b0bd05630b2c</email>
<email type="domain">u-bordeaux.fr</email>
</editor>
</titleStmt>
<editionStmt> <edition n="v1" type="current"> <date type="whenSubmitted">2015-10-14 14:18:30</date>
<date type="whenModified">2015-10-19 11:41:49</date>
<date type="whenReleased">2015-10-14 14:18:30</date>
<date type="whenProduced">2014-08-14</date>
</edition>
<respStmt> <resp>contributor</resp>
<name key="321070"> <persName> <forename>Chantal</forename>
<surname>GUERIN</surname>
</persName>
<email type="md5">eb4bde61f74652335183b0bd05630b2c</email>
<email type="domain">u-bordeaux.fr</email>
</name>
</respStmt>
</editionStmt>
<publicationStmt> <distributor>CCSD</distributor>
<idno type="halId">hal-01215533</idno>
<idno type="halUri">https://hal.archives-ouvertes.fr/hal-01215533</idno>
<idno type="halBibtex">bourdenx:hal-01215533</idno>
<idno type="halRefHtml">Frontiers in Neuroanatomy, Frontiers, 2014, <10.3389></idno>
<idno type="halRef">Frontiers in Neuroanatomy, Frontiers, 2014, <10.3389></idno>
</publicationStmt>
<seriesStmt> <idno type="stamp" n="CNRS">CNRS - Centre national de la recherche scientifique</idno>
</seriesStmt>
<notesStmt> <note type="audience" n="2">International</note>
<note type="popular" n="0">No</note>
<note type="peer" n="1">Yes</note>
</notesStmt>
<sourceDesc> <biblStruct> <analytic> <title xml:lang="en">Lysosomes and α-synuclein form a dangerous duet leading to neuronal cell death.</title>
<author role="aut"> <persName> <forename type="first">Mathieu</forename>
<surname>Bourdenx</surname>
</persName>
<idno type="halauthorid">1059960</idno>
<affiliation ref="#struct-244085"></affiliation>
</author>
<author role="aut"> <persName> <forename type="first">Erwan</forename>
<surname>Bezard</surname>
</persName>
<idno type="halauthorid">537314</idno>
<affiliation ref="#struct-244085"></affiliation>
</author>
<author role="aut"> <persName> <forename type="first">Benjamin</forename>
<surname>Dehay</surname>
</persName>
<idno type="halauthorid">159357</idno>
<affiliation ref="#struct-244085"></affiliation>
</author>
</analytic>
<monogr> <idno type="halJournalId" status="VALID">102181</idno>
<idno type="issn">1662-5129</idno>
<title level="j">Frontiers in Neuroanatomy</title>
<imprint> <publisher>Frontiers</publisher>
<date type="datePub">2014-08-14</date>
</imprint>
</monogr>
<idno type="pubmed">25177278</idno>
<idno type="doi">10.3389</idno>
</biblStruct>
</sourceDesc>
<profileDesc> <langUsage> <language ident="en">English</language>
</langUsage>
<textClass> <classCode scheme="halDomain" n="sdv">Life Sciences [q-bio]</classCode>
<classCode scheme="halTypology" n="ART">Journal articles</classCode>
</textClass>
<abstract xml:lang="en">Neurodegenerative diseases are (i) characterized by a selective neuronal vulnerability to degeneration in specific brain regions; and (ii) likely to be caused by disease-specific protein misfolding. Parkinson's disease (PD) is characterized by the presence of intraneuronal proteinacious cytoplasmic inclusions, called Lewy Bodies (LB). α-Synuclein, an aggregation prone protein, has been identified as a major protein component of LB and the causative for autosomal dominant PD. Lysosomes are responsible for the clearance of long-lived proteins, such as α-synuclein, and for the removal of old or damaged organelles, such as mitochondria. Interestingly, PD-linked α-synuclein mutants and dopamine-modified wild-type α-synuclein block its own degradation, which result in insufficient clearance, leading to its aggregation and cell toxicity. Moreover, both lysosomes and lysosomal proteases have been found to be involved in the activation of certain cell death pathways. Interestingly, lysosomal alterations are observed in the brains of patients suffering from sporadic PD and also in toxic and genetic rodent models of PD-related neurodegeneration. All these events have unraveled a causal link between lysosomal impairment, α-synuclein accumulation, and neurotoxicity. In this review, we emphasize the pathophysiological mechanisms connecting α-synuclein and lysosomal dysfunction in neuronal cell death.</abstract>
</profileDesc>
</hal>
</record>
Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Wicri/Sante/explor/ParkinsonFranceV1/Data/Hal/Corpus
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000648 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Hal/Corpus/biblio.hfd -nk 000648 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien |wiki= Wicri/Sante |area= ParkinsonFranceV1 |flux= Hal |étape= Corpus |type= RBID |clé= Hal:hal-01215533 |texte= Lysosomes and α-synuclein form a dangerous duet leading to neuronal cell death. }}
![]() | This area was generated with Dilib version V0.6.29. | ![]() |