Biochemical and pathological characterization of Lrrk2
Identifieur interne : 000748 ( Main/Corpus ); précédent : 000747; suivant : 000749Biochemical and pathological characterization of Lrrk2
Auteurs : Benoit I. Giasson ; Jason P. Covy ; Nancy M. Bonini ; Howard I. Hurtig ; Matthew J. Farrer ; John Q. Trojanowski ; Vivianna M. Van DeerlinSource :
- Annals of Neurology [ 0364-5134 ] ; 2006-02.
Abstract
Objective: Mutations in leucine‐rich repeat kinase 2 (LRRK2) recently have been identified as the most common genetic cause of late‐onset sporadic and familial Parkinson's disease (PD). The studies herein explore the biological and pathological properties of Lrrk2. Methods: Genetic analysis was performed to identify autopsied patients with the most common Lrrk2 mutation (G2019S). Using an antibody specific to Lrrk2, the biochemical and immunocytochemical distribution of Lrrk2 was assessed. Results: Three patients with the G2019S Lrrk2 mutation were identified. Two patients demonstrated classic PD with Lewy bodies, although concurrent pathological changes consistent with Alzheimer's disease were also present in one of these individuals. The third patient was characterized by parkinsonism without Lewy bodies but demonstrated dystrophic neurites in the substantia nigra intensely stained for Lrrk2. Lrrk2 accumulations were unique to this patient and Lrrk2 was not detected in other types of pathological inclusions. Biochemical analysis showed that Lrrk2 is predominantly a soluble approximately 250kDa cytoplasmic protein expressed throughout the brain but also in many other organs. Interpretation: The reasons for the selective predisposition of patients with mutations in LRRK2 to develop parkinsonism remains unclear, but Lrrk2 mutations may prime select neuronal populations to cellular insults that can lead to aberrant protein aggregation. Ann Neurol 2006;59:315–322
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DOI: 10.1002/ana.20791
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Bonini</name><affiliation><mods:affiliation>Department of Biology, Philadelphia, PA</mods:affiliation></affiliation><affiliation><mods:affiliation>Howard Hughes Medical Institute, Philadelphia, PA</mods:affiliation></affiliation></author><author><name sortKey="Hurtig, Howard I" sort="Hurtig, Howard I" uniqKey="Hurtig H" first="Howard I." last="Hurtig">Howard I. Hurtig</name><affiliation><mods:affiliation>Department of Neurology, Philadelphia, PA</mods:affiliation></affiliation></author><author><name sortKey="Farrer, Matthew J" sort="Farrer, Matthew J" uniqKey="Farrer M" first="Matthew J." last="Farrer">Matthew J. Farrer</name><affiliation><mods:affiliation>Department of Neuroscience, Mayo Clinic, Jacksonville, FL</mods:affiliation></affiliation></author><author><name sortKey="Trojanowski, John Q" sort="Trojanowski, John Q" uniqKey="Trojanowski J" first="John Q." last="Trojanowski">John Q. 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Giasson</name><affiliation><mods:affiliation>Department of Pharmacology, Philadelphia, PA</mods:affiliation></affiliation></author><author><name sortKey="Covy, Jason P" sort="Covy, Jason P" uniqKey="Covy J" first="Jason P." last="Covy">Jason P. Covy</name><affiliation><mods:affiliation>Department of Pharmacology, Philadelphia, PA</mods:affiliation></affiliation></author><author><name sortKey="Bonini, Nancy M" sort="Bonini, Nancy M" uniqKey="Bonini N" first="Nancy M." last="Bonini">Nancy M. Bonini</name><affiliation><mods:affiliation>Department of Biology, Philadelphia, PA</mods:affiliation></affiliation><affiliation><mods:affiliation>Howard Hughes Medical Institute, Philadelphia, PA</mods:affiliation></affiliation></author><author><name sortKey="Hurtig, Howard I" sort="Hurtig, Howard I" uniqKey="Hurtig H" first="Howard I." last="Hurtig">Howard I. Hurtig</name><affiliation><mods:affiliation>Department of Neurology, Philadelphia, PA</mods:affiliation></affiliation></author><author><name sortKey="Farrer, Matthew J" sort="Farrer, Matthew J" uniqKey="Farrer M" first="Matthew J." last="Farrer">Matthew J. Farrer</name><affiliation><mods:affiliation>Department of Neuroscience, Mayo Clinic, Jacksonville, FL</mods:affiliation></affiliation></author><author><name sortKey="Trojanowski, John Q" sort="Trojanowski, John Q" uniqKey="Trojanowski J" first="John Q." last="Trojanowski">John Q. Trojanowski</name><affiliation><mods:affiliation>Department of Pathology and Laboratory Medicine of the University of Pennsylvania, Philadelphia, PA</mods:affiliation></affiliation></author><author><name sortKey="Van Deerlin, Vivianna M" sort="Van Deerlin, Vivianna M" uniqKey="Van Deerlin V" first="Vivianna M." last="Van Deerlin">Vivianna M. Van Deerlin</name><affiliation><mods:affiliation>Department of Pathology and Laboratory Medicine of the University of Pennsylvania, Philadelphia, PA</mods:affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j">Annals of Neurology</title><title level="j" type="sub">Official Journal of the American Neurological Association and the Child Neurology Society</title><title level="j" type="abbrev">Ann Neurol.</title><idno type="ISSN">0364-5134</idno><idno type="eISSN">1531-8249</idno><imprint><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>Hoboken</pubPlace><date type="published" when="2006-02">2006-02</date><biblScope unit="volume">59</biblScope><biblScope unit="issue">2</biblScope><biblScope unit="page" from="315">315</biblScope><biblScope unit="page" to="322">322</biblScope></imprint><idno type="ISSN">0364-5134</idno></series><idno type="istex">F58D0606F4849FFB9BB4573BE664D9729F4D1A7F</idno><idno type="DOI">10.1002/ana.20791</idno><idno type="ArticleID">ANA20791</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0364-5134</idno></seriesStmt></fileDesc><profileDesc><textClass></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Objective: Mutations in leucine‐rich repeat kinase 2 (LRRK2) recently have been identified as the most common genetic cause of late‐onset sporadic and familial Parkinson's disease (PD). The studies herein explore the biological and pathological properties of Lrrk2. Methods: Genetic analysis was performed to identify autopsied patients with the most common Lrrk2 mutation (G2019S). Using an antibody specific to Lrrk2, the biochemical and immunocytochemical distribution of Lrrk2 was assessed. Results: Three patients with the G2019S Lrrk2 mutation were identified. Two patients demonstrated classic PD with Lewy bodies, although concurrent pathological changes consistent with Alzheimer's disease were also present in one of these individuals. The third patient was characterized by parkinsonism without Lewy bodies but demonstrated dystrophic neurites in the substantia nigra intensely stained for Lrrk2. Lrrk2 accumulations were unique to this patient and Lrrk2 was not detected in other types of pathological inclusions. Biochemical analysis showed that Lrrk2 is predominantly a soluble approximately 250kDa cytoplasmic protein expressed throughout the brain but also in many other organs. Interpretation: The reasons for the selective predisposition of patients with mutations in LRRK2 to develop parkinsonism remains unclear, but Lrrk2 mutations may prime select neuronal populations to cellular insults that can lead to aberrant protein aggregation. Ann Neurol 2006;59:315–322</div></front></TEI><istex><corpusName>wiley</corpusName><author><json:item><name>Benoit I. Giasson PhD</name><affiliations><json:string>Department of Pharmacology, Philadelphia, PA</json:string></affiliations></json:item><json:item><name>Jason P. Covy BS</name><affiliations><json:string>Department of Pharmacology, Philadelphia, PA</json:string></affiliations></json:item><json:item><name>Nancy M. Bonini PhD</name><affiliations><json:string>Department of Biology, Philadelphia, PA</json:string><json:string>Howard Hughes Medical Institute, Philadelphia, PA</json:string></affiliations></json:item><json:item><name>Howard I. Hurtig MD</name><affiliations><json:string>Department of Neurology, Philadelphia, PA</json:string></affiliations></json:item><json:item><name>Matthew J. Farrer PhD</name><affiliations><json:string>Department of Neuroscience, Mayo Clinic, Jacksonville, FL</json:string></affiliations></json:item><json:item><name>John Q. Trojanowski MD, PhD</name><affiliations><json:string>Department of Pathology and Laboratory Medicine of the University of Pennsylvania, Philadelphia, PA</json:string></affiliations></json:item><json:item><name>Vivianna M. Van Deerlin MD, PhD</name><affiliations><json:string>Department of Pathology and Laboratory Medicine of the University of Pennsylvania, Philadelphia, PA</json:string></affiliations></json:item></author><articleId><json:string>ANA20791</json:string></articleId><language><json:string>eng</json:string></language><abstract>Objective: Mutations in leucine‐rich repeat kinase 2 (LRRK2) recently have been identified as the most common genetic cause of late‐onset sporadic and familial Parkinson's disease (PD). The studies herein explore the biological and pathological properties of Lrrk2. Methods: Genetic analysis was performed to identify autopsied patients with the most common Lrrk2 mutation (G2019S). Using an antibody specific to Lrrk2, the biochemical and immunocytochemical distribution of Lrrk2 was assessed. Results: Three patients with the G2019S Lrrk2 mutation were identified. Two patients demonstrated classic PD with Lewy bodies, although concurrent pathological changes consistent with Alzheimer's disease were also present in one of these individuals. The third patient was characterized by parkinsonism without Lewy bodies but demonstrated dystrophic neurites in the substantia nigra intensely stained for Lrrk2. Lrrk2 accumulations were unique to this patient and Lrrk2 was not detected in other types of pathological inclusions. Biochemical analysis showed that Lrrk2 is predominantly a soluble approximately 250kDa cytoplasmic protein expressed throughout the brain but also in many other organs. Interpretation: The reasons for the selective predisposition of patients with mutations in LRRK2 to develop parkinsonism remains unclear, but Lrrk2 mutations may prime select neuronal populations to cellular insults that can lead to aberrant protein aggregation. 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No. AG10124; No. AG17586; No. NS044233;</note></notesStmt><sourceDesc><biblStruct type="inbook"><analytic><title level="a" type="main" xml:lang="en">Biochemical and pathological characterization of Lrrk2</title><author><persName><forename type="first">Benoit I.</forename><surname>Giasson</surname></persName><roleName type="degree">PhD</roleName><note type="correspondence"><p>Correspondence: Department of Pharmacology, University of Pennsylvania School of Medicine, 3620 Hamilton Walk, 164 John Morgan Building, Philadelphia, PA 19104‐6084</p></note><affiliation>Department of Pharmacology, Philadelphia, PA</affiliation></author><author><persName><forename type="first">Jason P.</forename><surname>Covy</surname></persName><roleName type="degree">BS</roleName><affiliation>Department of Pharmacology, Philadelphia, PA</affiliation></author><author><persName><forename type="first">Nancy M.</forename><surname>Bonini</surname></persName><roleName type="degree">PhD</roleName><affiliation>Department of Biology, Philadelphia, PA</affiliation><affiliation>Howard Hughes Medical Institute, Philadelphia, PA</affiliation></author><author><persName><forename type="first">Howard I.</forename><surname>Hurtig</surname></persName><roleName type="degree">MD</roleName><affiliation>Department of Neurology, Philadelphia, PA</affiliation></author><author><persName><forename type="first">Matthew J.</forename><surname>Farrer</surname></persName><roleName type="degree">PhD</roleName><affiliation>Department of Neuroscience, Mayo Clinic, Jacksonville, FL</affiliation></author><author><persName><forename type="first">John Q.</forename><surname>Trojanowski</surname></persName><roleName type="degree">MD, PhD</roleName><affiliation>Department of Pathology and Laboratory Medicine of the University of Pennsylvania, Philadelphia, PA</affiliation></author><author><persName><forename type="first">Vivianna M.</forename><surname>Van Deerlin</surname></persName><roleName type="degree">MD, PhD</roleName><affiliation>Department of Pathology and Laboratory Medicine of the University of Pennsylvania, Philadelphia, PA</affiliation></author></analytic><monogr><title level="j">Annals of Neurology</title><title level="j" type="sub">Official Journal of the American Neurological Association and the Child Neurology Society</title><title level="j" type="abbrev">Ann Neurol.</title><idno type="pISSN">0364-5134</idno><idno type="eISSN">1531-8249</idno><idno type="DOI">10.1002/(ISSN)1531-8249</idno><imprint><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>Hoboken</pubPlace><date type="published" when="2006-02"></date><biblScope unit="volume">59</biblScope><biblScope unit="issue">2</biblScope><biblScope unit="page" from="315">315</biblScope><biblScope unit="page" to="322">322</biblScope></imprint></monogr><idno type="istex">F58D0606F4849FFB9BB4573BE664D9729F4D1A7F</idno><idno type="DOI">10.1002/ana.20791</idno><idno type="ArticleID">ANA20791</idno></biblStruct></sourceDesc></fileDesc><profileDesc><creation><date>2006</date></creation><langUsage><language ident="en">en</language></langUsage><abstract xml:lang="en"><p>Objective: Mutations in leucine‐rich repeat kinase 2 (LRRK2) recently have been identified as the most common genetic cause of late‐onset sporadic and familial Parkinson's disease (PD). The studies herein explore the biological and pathological properties of Lrrk2. Methods: Genetic analysis was performed to identify autopsied patients with the most common Lrrk2 mutation (G2019S). Using an antibody specific to Lrrk2, the biochemical and immunocytochemical distribution of Lrrk2 was assessed. Results: Three patients with the G2019S Lrrk2 mutation were identified. Two patients demonstrated classic PD with Lewy bodies, although concurrent pathological changes consistent with Alzheimer's disease were also present in one of these individuals. The third patient was characterized by parkinsonism without Lewy bodies but demonstrated dystrophic neurites in the substantia nigra intensely stained for Lrrk2. Lrrk2 accumulations were unique to this patient and Lrrk2 was not detected in other types of pathological inclusions. Biochemical analysis showed that Lrrk2 is predominantly a soluble approximately 250kDa cytoplasmic protein expressed throughout the brain but also in many other organs. Interpretation: The reasons for the selective predisposition of patients with mutations in LRRK2 to develop parkinsonism remains unclear, but Lrrk2 mutations may prime select neuronal populations to cellular insults that can lead to aberrant protein aggregation. Ann Neurol 2006;59:315–322</p></abstract><textClass><keywords scheme="Journal Subject"><list><head>article category</head><item><term>Original Article</term></item></list></keywords></textClass></profileDesc><revisionDesc><change when="2005-08-30">Received</change><change when="2005-12-02">Registration</change><change when="2006-02">Published</change></revisionDesc></teiHeader></istex:fulltextTEI><json:item><original>false</original><mimetype>text/plain</mimetype><extension>txt</extension><uri>https://api.istex.fr/document/F58D0606F4849FFB9BB4573BE664D9729F4D1A7F/fulltext/txt</uri></json:item></fulltext><metadata><istex:metadataXml wicri:clean="Wiley, elements deleted: body"><istex:xmlDeclaration>version="1.0" encoding="UTF-8" standalone="yes"</istex:xmlDeclaration><istex:document><component version="2.0" type="serialArticle" xml:lang="en"><header><publicationMeta level="product"><publisherInfo><publisherName>Wiley Subscription Services, Inc., A Wiley 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affiliationRef="#af1" corresponding="yes"><personName><givenNames>Benoit I.</givenNames><familyName>Giasson</familyName><degrees>PhD</degrees></personName><contactDetails><email>giassonb@mail.med.upenn.edu</email></contactDetails></creator><creator xml:id="au2" creatorRole="author" affiliationRef="#af1"><personName><givenNames>Jason P.</givenNames><familyName>Covy</familyName><degrees>BS</degrees></personName></creator><creator xml:id="au3" creatorRole="author" affiliationRef="#af2 #af3"><personName><givenNames>Nancy M.</givenNames><familyName>Bonini</familyName><degrees>PhD</degrees></personName></creator><creator xml:id="au4" creatorRole="author" affiliationRef="#af4"><personName><givenNames>Howard I.</givenNames><familyName>Hurtig</familyName><degrees>MD</degrees></personName></creator><creator xml:id="au5" creatorRole="author" affiliationRef="#af6"><personName><givenNames>Matthew J.</givenNames><familyName>Farrer</familyName><degrees>PhD</degrees></personName></creator><creator xml:id="au6" creatorRole="author" affiliationRef="#af5"><personName><givenNames>John Q.</givenNames><familyName>Trojanowski</familyName><degrees>MD, PhD</degrees></personName></creator><creator xml:id="au7" creatorRole="author" affiliationRef="#af5"><personName><givenNames>Vivianna M.</givenNames><familyName>Van Deerlin</familyName><degrees>MD, PhD</degrees></personName></creator></creators><affiliationGroup><affiliation xml:id="af1" countryCode="US" type="organization"><unparsedAffiliation>Department of Pharmacology, Philadelphia, PA</unparsedAffiliation></affiliation><affiliation xml:id="af2" countryCode="US" type="organization"><unparsedAffiliation>Department of Biology, Philadelphia, PA</unparsedAffiliation></affiliation><affiliation xml:id="af3" countryCode="US" type="organization"><unparsedAffiliation>Howard Hughes Medical Institute, Philadelphia, PA</unparsedAffiliation></affiliation><affiliation xml:id="af4" countryCode="US" type="organization"><unparsedAffiliation>Department of Neurology, Philadelphia, PA</unparsedAffiliation></affiliation><affiliation xml:id="af5" countryCode="US" type="organization"><unparsedAffiliation>Department of Pathology and Laboratory Medicine of the University of Pennsylvania, Philadelphia, PA</unparsedAffiliation></affiliation><affiliation xml:id="af6" countryCode="US" type="organization"><unparsedAffiliation>Department of Neuroscience, Mayo Clinic, Jacksonville, FL</unparsedAffiliation></affiliation></affiliationGroup><fundingInfo><fundingAgency>NIH (National Institute on Aging and National Institute of Neurological Disorders and Stroke)</fundingAgency><fundingNumber>AG09215</fundingNumber><fundingNumber>AG10124</fundingNumber><fundingNumber>AG17586</fundingNumber><fundingNumber>NS044233</fundingNumber></fundingInfo><abstractGroup><abstract type="main" xml:lang="en"><title type="main">Abstract</title><section xml:id="abs1-1"><title type="main">Objective</title><p>Mutations in leucine‐rich repeat kinase 2 (<i>LRRK2</i>) recently have been identified as the most common genetic cause of late‐onset sporadic and familial Parkinson's disease (PD). The studies herein explore the biological and pathological properties of Lrrk2.</p></section><section xml:id="abs1-2"><title type="main">Methods</title><p>Genetic analysis was performed to identify autopsied patients with the most common Lrrk2 mutation (G2019S). Using an antibody specific to Lrrk2, the biochemical and immunocytochemical distribution of Lrrk2 was assessed.</p></section><section xml:id="abs1-3"><title type="main">Results</title><p>Three patients with the G2019S Lrrk2 mutation were identified. Two patients demonstrated classic PD with Lewy bodies, although concurrent pathological changes consistent with Alzheimer's disease were also present in one of these individuals. The third patient was characterized by parkinsonism without Lewy bodies but demonstrated dystrophic neurites in the substantia nigra intensely stained for Lrrk2. Lrrk2 accumulations were unique to this patient and Lrrk2 was not detected in other types of pathological inclusions. Biochemical analysis showed that Lrrk2 is predominantly a soluble approximately 250kDa cytoplasmic protein expressed throughout the brain but also in many other organs.</p></section><section xml:id="abs1-4"><title type="main">Interpretation</title><p>The reasons for the selective predisposition of patients with mutations in <i>LRRK2</i> to develop parkinsonism remains unclear, but Lrrk2 mutations may prime select neuronal populations to cellular insults that can lead to aberrant protein aggregation. Ann Neurol 2006;59:315–322</p></section></abstract></abstractGroup></contentMeta></header></component></istex:document></istex:metadataXml><mods version="3.6"><titleInfo lang="en"><title>Biochemical and pathological characterization of Lrrk2</title></titleInfo><titleInfo type="abbreviated" lang="en"><title>Characterization of Lrrk2</title></titleInfo><titleInfo type="alternative" contentType="CDATA" lang="en"><title>Biochemical and pathological characterization of Lrrk2</title></titleInfo><name type="personal"><namePart type="given">Benoit I.</namePart><namePart type="family">Giasson</namePart><namePart type="termsOfAddress">PhD</namePart><affiliation>Department of Pharmacology, Philadelphia, PA</affiliation><description>Correspondence: Department of Pharmacology, University of Pennsylvania School of Medicine, 3620 Hamilton Walk, 164 John Morgan Building, Philadelphia, PA 19104‐6084</description><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Jason P.</namePart><namePart type="family">Covy</namePart><namePart type="termsOfAddress">BS</namePart><affiliation>Department of Pharmacology, Philadelphia, PA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Nancy M.</namePart><namePart type="family">Bonini</namePart><namePart type="termsOfAddress">PhD</namePart><affiliation>Department of Biology, Philadelphia, PA</affiliation><affiliation>Howard Hughes Medical Institute, Philadelphia, PA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Howard I.</namePart><namePart type="family">Hurtig</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Department of Neurology, Philadelphia, PA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Matthew J.</namePart><namePart type="family">Farrer</namePart><namePart type="termsOfAddress">PhD</namePart><affiliation>Department of Neuroscience, Mayo Clinic, Jacksonville, FL</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">John Q.</namePart><namePart type="family">Trojanowski</namePart><namePart type="termsOfAddress">MD, PhD</namePart><affiliation>Department of Pathology and Laboratory Medicine of the University of Pennsylvania, Philadelphia, PA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Vivianna M.</namePart><namePart type="family">Van Deerlin</namePart><namePart type="termsOfAddress">MD, PhD</namePart><affiliation>Department of Pathology and Laboratory Medicine of the University of Pennsylvania, Philadelphia, PA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="article" displayLabel="article"></genre><originInfo><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><place><placeTerm type="text">Hoboken</placeTerm></place><dateIssued encoding="w3cdtf">2006-02</dateIssued><dateCaptured encoding="w3cdtf">2005-08-30</dateCaptured><dateValid encoding="w3cdtf">2005-12-02</dateValid><copyrightDate encoding="w3cdtf">2006</copyrightDate></originInfo><language><languageTerm type="code" authority="rfc3066">en</languageTerm><languageTerm type="code" authority="iso639-2b">eng</languageTerm></language><physicalDescription><internetMediaType>text/html</internetMediaType><extent unit="figures">2</extent><extent unit="tables">1</extent><extent unit="references">30</extent><extent unit="words">5421</extent></physicalDescription><abstract lang="en">Objective: Mutations in leucine‐rich repeat kinase 2 (LRRK2) recently have been identified as the most common genetic cause of late‐onset sporadic and familial Parkinson's disease (PD). The studies herein explore the biological and pathological properties of Lrrk2. Methods: Genetic analysis was performed to identify autopsied patients with the most common Lrrk2 mutation (G2019S). Using an antibody specific to Lrrk2, the biochemical and immunocytochemical distribution of Lrrk2 was assessed. Results: Three patients with the G2019S Lrrk2 mutation were identified. Two patients demonstrated classic PD with Lewy bodies, although concurrent pathological changes consistent with Alzheimer's disease were also present in one of these individuals. The third patient was characterized by parkinsonism without Lewy bodies but demonstrated dystrophic neurites in the substantia nigra intensely stained for Lrrk2. Lrrk2 accumulations were unique to this patient and Lrrk2 was not detected in other types of pathological inclusions. Biochemical analysis showed that Lrrk2 is predominantly a soluble approximately 250kDa cytoplasmic protein expressed throughout the brain but also in many other organs. Interpretation: The reasons for the selective predisposition of patients with mutations in LRRK2 to develop parkinsonism remains unclear, but Lrrk2 mutations may prime select neuronal populations to cellular insults that can lead to aberrant protein aggregation. Ann Neurol 2006;59:315–322</abstract><note type="funding">NIH (National Institute on Aging and National Institute of Neurological Disorders and Stroke) - No. AG09215; No. AG10124; No. AG17586; No. NS044233; </note><relatedItem type="host"><titleInfo><title>Annals of Neurology</title><subTitle>Official Journal of the American Neurological Association and the Child Neurology Society</subTitle></titleInfo><titleInfo type="abbreviated"><title>Ann Neurol.</title></titleInfo><genre type="Journal">journal</genre><subject><genre>article category</genre><topic>Original Article</topic></subject><identifier type="ISSN">0364-5134</identifier><identifier type="eISSN">1531-8249</identifier><identifier type="DOI">10.1002/(ISSN)1531-8249</identifier><identifier type="PublisherID">ANA</identifier><part><date>2006</date><detail type="volume"><caption>vol.</caption><number>59</number></detail><detail type="issue"><caption>no.</caption><number>2</number></detail><extent unit="pages"><start>315</start><end>322</end><total>8</total></extent></part></relatedItem><identifier type="istex">F58D0606F4849FFB9BB4573BE664D9729F4D1A7F</identifier><identifier type="DOI">10.1002/ana.20791</identifier><identifier type="ArticleID">ANA20791</identifier><accessCondition type="use and reproduction" contentType="copyright">Copyright © 2006 American Neurological Association</accessCondition><recordInfo><recordContentSource>WILEY</recordContentSource><recordOrigin>Wiley Subscription Services, Inc., A Wiley Company</recordOrigin></recordInfo></mods></metadata><serie></serie></istex></record>Pour manipuler ce document sous Unix (Dilib)
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