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Mechanisms in dominant parkinsonism: The toxic triangle of LRRK2, α‐synuclein, and tau

Identifieur interne : 000B79 ( Main/Corpus ); précédent : 000B78; suivant : 000B80

Mechanisms in dominant parkinsonism: The toxic triangle of LRRK2, α‐synuclein, and tau

Auteurs : Jean-Marc Taymans ; Mark R. Cookson

Source :

RBID : ISTEX:BAD8011D8F2673D5ABA6187FCDF1135776A1DE8E

English descriptors

Abstract

Parkinson's disease (PD) is generally sporadic but a number of genetic diseases have parkinsonism as a clinical feature. Two dominant genes, α‐synuclein (SNCA) and leucine‐rich repeat kinase 2 (LRRK2), are important for understanding inherited and sporadic PD. SNCA is a major component of pathologic inclusions termed Lewy bodies found in PD. LRRK2 is found in a significant proportion of PD cases. These two proteins may be linked as most LRRK2 PD cases have SNCA‐positive Lewy bodies. Mutations in both proteins are associated with toxic effects in model systems although mechanisms are unclear. LRRK2 is an intracellular signaling protein possessing both GTPase and kinase activities that may contribute to pathogenicity. A third protein, tau, is implicated as a risk factor for PD. We discuss the potential relationship between these genes and suggest a model for PD pathogenesis where LRRK2 is upstream of pathogenic effects through SNCA, tau, or both proteins.

Url:
DOI: 10.1002/bies.200900163

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ISTEX:BAD8011D8F2673D5ABA6187FCDF1135776A1DE8E

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<abstract lang="en">Parkinson's disease (PD) is generally sporadic but a number of genetic diseases have parkinsonism as a clinical feature. Two dominant genes, α‐synuclein (SNCA) and leucine‐rich repeat kinase 2 (LRRK2), are important for understanding inherited and sporadic PD. SNCA is a major component of pathologic inclusions termed Lewy bodies found in PD. LRRK2 is found in a significant proportion of PD cases. These two proteins may be linked as most LRRK2 PD cases have SNCA‐positive Lewy bodies. Mutations in both proteins are associated with toxic effects in model systems although mechanisms are unclear. LRRK2 is an intracellular signaling protein possessing both GTPase and kinase activities that may contribute to pathogenicity. A third protein, tau, is implicated as a risk factor for PD. We discuss the potential relationship between these genes and suggest a model for PD pathogenesis where LRRK2 is upstream of pathogenic effects through SNCA, tau, or both proteins.</abstract>
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<genre>Keywords</genre>
<topic>genetics</topic>
<topic>kinases</topic>
<topic>microtubule</topic>
<topic>neurodegeneration</topic>
<topic>Parkinson's disease</topic>
<topic>synapse</topic>
</subject>
<relatedItem type="host">
<titleInfo>
<title>BioEssays</title>
</titleInfo>
<titleInfo type="abbreviated">
<title>Bioessays</title>
</titleInfo>
<genre type="Journal">journal</genre>
<subject>
<genre>article category</genre>
<topic>Problems and paradigms</topic>
</subject>
<identifier type="ISSN">0265-9247</identifier>
<identifier type="eISSN">1521-1878</identifier>
<identifier type="DOI">10.1002/(ISSN)1521-1878</identifier>
<identifier type="PublisherID">BIES</identifier>
<part>
<date>2010</date>
<detail type="volume">
<caption>vol.</caption>
<number>32</number>
</detail>
<detail type="issue">
<caption>no.</caption>
<number>3</number>
</detail>
<extent unit="pages">
<start>227</start>
<end>235</end>
<total>9</total>
</extent>
</part>
</relatedItem>
<identifier type="istex">BAD8011D8F2673D5ABA6187FCDF1135776A1DE8E</identifier>
<identifier type="DOI">10.1002/bies.200900163</identifier>
<identifier type="ArticleID">BIES200900163</identifier>
<accessCondition type="use and reproduction" contentType="copyright">Copyright © 2010 Wiley Periodicals, Inc.</accessCondition>
<recordInfo>
<recordContentSource>WILEY</recordContentSource>
<recordOrigin>WILEY‐VCH Verlag</recordOrigin>
</recordInfo>
</mods>
</metadata>
<serie></serie>
</istex>
</record>

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   |texte=   Mechanisms in dominant parkinsonism: The toxic triangle of LRRK2, α‐synuclein, and tau
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