The Degeneration of Dopamine Neurons in Parkinson's Disease: Insights from Embryology and Evolution of the Mesostriatocortical System
Identifieur interne : 001F00 ( Istex/Corpus ); précédent : 001E99; suivant : 001F01The Degeneration of Dopamine Neurons in Parkinson's Disease: Insights from Embryology and Evolution of the Mesostriatocortical System
Auteurs : Philippe Vernier ; Frederic Moret ; Sophie Callier ; Marina Snapyan ; Christophe Wersinger ; Anita SidhuSource :
- Annals of the New York Academy of Sciences [ 0077-8923 ] ; 2004-12.
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Abstract
Abstract: Parkinson's disease (PD) is, to a large extent, specific to the human species. Most symptoms are the consequence of the preferential degeneration of the dopamine‐synthesizing cells of the mesostriatal‐mesocortical neuronal pathway. Reasons for that can be traced back to the evolutionary mechanisms that shaped the dopamine neurons in humans. In vertebrates, dopamine‐containing neurons and nuclei do not exhibit homogenous phenotypes. In this respect, mesencephalic dopamine neurons of the substantia nigra and ventral tegmental area are characterized by a molecular combination (tyrosine hydroxylase, aromatic amino acid decarboxylase, monoamine oxidase, vesicular monoamine transporter, dopamine transporter—to name a few), which is not found in other dopamine‐containing neurons of the vertebrate brain. In addition, the size of these mesencephalic DA nuclei is tremendously expanded in humans as compared to other vertebrates. Differentiation of the mesencephalic neurons during development depends on genetic mechanisms, which also differ from those of other dopamine nuclei. In contrast, pathophysiological approaches to PD have highlighted the role of ubiquitously expressed molecules such as a‐synuclein, parkin, and microtubule‐associated proteins. We propose that the peculiar phenotype of the dopamine mesencephalic neurons, which has been selected during vertebrate evolution and reshaped in the human lineage, has also rendered these neurons particularly prone to oxidative stress, and thus, to the fairly specific neurodegeneration of PD. Numerous evidence has been accumulated to demonstrate that perturbed regulation of DAT‐dependent dopamine uptake, DAT‐dependent accumulation of toxins, dysregulation of TH activity as well as high sensitivity of DA mesencephalic neurons to oxidants are key components of the neurodegeneration process of PD. This view points to the contribution of nonspecific mechanisms (α‐synuclein aggregation) in a highly specific cellular environment (the dopamine mesencephalic neurons) and provides a robust framework to develop novel and rational therapeutic schemes in PD.
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DOI: 10.1196/annals.1332.015
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Fessard, CNRS, 91198 Gif‐sur‐Yvette, France</mods:affiliation></affiliation><affiliation><mods:affiliation>E-mail: vernier@iaf.cnrs‐gif.fr</mods:affiliation></affiliation></author><author><name sortKey="Moret, Frederic" sort="Moret, Frederic" uniqKey="Moret F" first="Frederic" last="Moret">Frederic Moret</name><affiliation><mods:affiliation>Development, Evolution, Plasticity of the Nervous System, Institute of Neurobiology A. Fessard, CNRS, 91198 Gif‐sur‐Yvette, France</mods:affiliation></affiliation></author><author><name sortKey="Callier, Sophie" sort="Callier, Sophie" uniqKey="Callier S" first="Sophie" last="Callier">Sophie Callier</name><affiliation><mods:affiliation>Development, Evolution, Plasticity of the Nervous System, Institute of Neurobiology A. Fessard, CNRS, 91198 Gif‐sur‐Yvette, France</mods:affiliation></affiliation></author><author><name sortKey="Snapyan, Marina" sort="Snapyan, Marina" uniqKey="Snapyan M" first="Marina" last="Snapyan">Marina Snapyan</name><affiliation><mods:affiliation>Development, Evolution, Plasticity of the Nervous System, Institute of Neurobiology A. Fessard, CNRS, 91198 Gif‐sur‐Yvette, France</mods:affiliation></affiliation></author><author><name sortKey="Wersinger, Christophe" sort="Wersinger, Christophe" uniqKey="Wersinger C" first="Christophe" last="Wersinger">Christophe Wersinger</name><affiliation><mods:affiliation>Department of Pediatrics, Georgetown University, Washington, District of Columbia 20007, USA</mods:affiliation></affiliation></author><author><name sortKey="Sidhu, Anita" sort="Sidhu, Anita" uniqKey="Sidhu A" first="Anita" last="Sidhu">Anita Sidhu</name><affiliation><mods:affiliation>Department of Pediatrics, Georgetown University, Washington, District of Columbia 20007, USA</mods:affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j">Annals of the New York Academy of Sciences</title><idno type="ISSN">0077-8923</idno><idno type="eISSN">1749-6632</idno><imprint><publisher>Blackwell Publishing Ltd</publisher><pubPlace>Oxford, UK</pubPlace><date type="published" when="2004-12">2004-12</date><biblScope unit="volume">1035</biblScope><biblScope unit="issue">1</biblScope><biblScope unit="page" from="231">231</biblScope><biblScope unit="page" to="249">249</biblScope></imprint><idno type="ISSN">0077-8923</idno></series><idno type="istex">5B1D38C926A4F3FC8CDDF8DB627F9D146974C8D4</idno><idno type="DOI">10.1196/annals.1332.015</idno><idno type="ArticleID">NYAS231</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0077-8923</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Parkinson's disease (PD)</term><term>development</term><term>dopamine receptors</term><term>dopamine transporter</term><term>neuroprotection</term><term>α‐synuclein</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract">Abstract: Parkinson's disease (PD) is, to a large extent, specific to the human species. Most symptoms are the consequence of the preferential degeneration of the dopamine‐synthesizing cells of the mesostriatal‐mesocortical neuronal pathway. Reasons for that can be traced back to the evolutionary mechanisms that shaped the dopamine neurons in humans. In vertebrates, dopamine‐containing neurons and nuclei do not exhibit homogenous phenotypes. In this respect, mesencephalic dopamine neurons of the substantia nigra and ventral tegmental area are characterized by a molecular combination (tyrosine hydroxylase, aromatic amino acid decarboxylase, monoamine oxidase, vesicular monoamine transporter, dopamine transporter—to name a few), which is not found in other dopamine‐containing neurons of the vertebrate brain. In addition, the size of these mesencephalic DA nuclei is tremendously expanded in humans as compared to other vertebrates. Differentiation of the mesencephalic neurons during development depends on genetic mechanisms, which also differ from those of other dopamine nuclei. In contrast, pathophysiological approaches to PD have highlighted the role of ubiquitously expressed molecules such as a‐synuclein, parkin, and microtubule‐associated proteins. We propose that the peculiar phenotype of the dopamine mesencephalic neurons, which has been selected during vertebrate evolution and reshaped in the human lineage, has also rendered these neurons particularly prone to oxidative stress, and thus, to the fairly specific neurodegeneration of PD. Numerous evidence has been accumulated to demonstrate that perturbed regulation of DAT‐dependent dopamine uptake, DAT‐dependent accumulation of toxins, dysregulation of TH activity as well as high sensitivity of DA mesencephalic neurons to oxidants are key components of the neurodegeneration process of PD. This view points to the contribution of nonspecific mechanisms (α‐synuclein aggregation) in a highly specific cellular environment (the dopamine mesencephalic neurons) and provides a robust framework to develop novel and rational therapeutic schemes in PD.</div></front></TEI><istex><corpusName>wiley</corpusName><author><json:item><name>PHILIPPE VERNIER</name><affiliations><json:string>Development, Evolution, Plasticity of the Nervous System, Institute of Neurobiology A. Fessard, CNRS, 91198 Gif‐sur‐Yvette, France</json:string><json:string>E-mail: vernier@iaf.cnrs‐gif.fr</json:string></affiliations></json:item><json:item><name>FREDERIC MORET</name><affiliations><json:string>Development, Evolution, Plasticity of the Nervous System, Institute of Neurobiology A. Fessard, CNRS, 91198 Gif‐sur‐Yvette, France</json:string></affiliations></json:item><json:item><name>SOPHIE CALLIER</name><affiliations><json:string>Development, Evolution, Plasticity of the Nervous System, Institute of Neurobiology A. Fessard, CNRS, 91198 Gif‐sur‐Yvette, France</json:string></affiliations></json:item><json:item><name>MARINA SNAPYAN</name><affiliations><json:string>Development, Evolution, Plasticity of the Nervous System, Institute of Neurobiology A. Fessard, CNRS, 91198 Gif‐sur‐Yvette, France</json:string></affiliations></json:item><json:item><name>CHRISTOPHE WERSINGER</name><affiliations><json:string>Department of Pediatrics, Georgetown University, Washington, District of Columbia 20007, USA</json:string></affiliations></json:item><json:item><name>ANITA SIDHU</name><affiliations><json:string>Department of Pediatrics, Georgetown University, Washington, District of Columbia 20007, USA</json:string></affiliations></json:item></author><subject><json:item><lang><json:string>eng</json:string></lang><value>Parkinson's disease (PD)</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>development</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>dopamine transporter</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>dopamine receptors</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>α‐synuclein</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>neuroprotection</value></json:item></subject><articleId><json:string>NYAS231</json:string></articleId><language><json:string>eng</json:string></language><originalGenre><json:string>article</json:string></originalGenre><abstract>Abstract: Parkinson's disease (PD) is, to a large extent, specific to the human species. Most symptoms are the consequence of the preferential degeneration of the dopamine‐synthesizing cells of the mesostriatal‐mesocortical neuronal pathway. Reasons for that can be traced back to the evolutionary mechanisms that shaped the dopamine neurons in humans. In vertebrates, dopamine‐containing neurons and nuclei do not exhibit homogenous phenotypes. In this respect, mesencephalic dopamine neurons of the substantia nigra and ventral tegmental area are characterized by a molecular combination (tyrosine hydroxylase, aromatic amino acid decarboxylase, monoamine oxidase, vesicular monoamine transporter, dopamine transporter—to name a few), which is not found in other dopamine‐containing neurons of the vertebrate brain. In addition, the size of these mesencephalic DA nuclei is tremendously expanded in humans as compared to other vertebrates. Differentiation of the mesencephalic neurons during development depends on genetic mechanisms, which also differ from those of other dopamine nuclei. In contrast, pathophysiological approaches to PD have highlighted the role of ubiquitously expressed molecules such as a‐synuclein, parkin, and microtubule‐associated proteins. We propose that the peculiar phenotype of the dopamine mesencephalic neurons, which has been selected during vertebrate evolution and reshaped in the human lineage, has also rendered these neurons particularly prone to oxidative stress, and thus, to the fairly specific neurodegeneration of PD. Numerous evidence has been accumulated to demonstrate that perturbed regulation of DAT‐dependent dopamine uptake, DAT‐dependent accumulation of toxins, dysregulation of TH activity as well as high sensitivity of DA mesencephalic neurons to oxidants are key components of the neurodegeneration process of PD. This view points to the contribution of nonspecific mechanisms (α‐synuclein aggregation) in a highly specific cellular environment (the dopamine mesencephalic neurons) and provides a robust framework to develop novel and rational therapeutic schemes in PD.</abstract><qualityIndicators><score>8</score><pdfVersion>1.3</pdfVersion><pdfPageSize>432 x 648 pts</pdfPageSize><refBibsNative>true</refBibsNative><abstractCharCount>2128</abstractCharCount><pdfWordCount>8766</pdfWordCount><pdfCharCount>54996</pdfCharCount><pdfPageCount>19</pdfPageCount><abstractWordCount>289</abstractWordCount></qualityIndicators><title>The Degeneration of Dopamine Neurons in Parkinson's Disease: Insights from Embryology and Evolution of the Mesostriatocortical System</title><refBibs><json:item><author><json:item><name>J.M. 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Brain</title></host><title>The substantia nigra of the human brain</title></json:item></refBibs><genre><json:string>article</json:string></genre><host><volume>1035</volume><publisherId><json:string>NYAS</json:string></publisherId><pages><total>19</total><last>249</last><first>231</first></pages><issn><json:string>0077-8923</json:string></issn><issue>1</issue><genre><json:string>journal</json:string></genre><language><json:string>unknown</json:string></language><eissn><json:string>1749-6632</json:string></eissn><title>Annals of the New York Academy of Sciences</title><doi><json:string>10.1111/(ISSN)1749-6632</json:string></doi></host><categories><wos><json:string>science</json:string><json:string>multidisciplinary sciences</json:string></wos><scienceMetrix><json:string>general</json:string><json:string>general science & technology</json:string><json:string>general science & technology</json:string></scienceMetrix></categories><publicationDate>2004</publicationDate><copyrightDate>2004</copyrightDate><doi><json:string>10.1196/annals.1332.015</json:string></doi><id>5B1D38C926A4F3FC8CDDF8DB627F9D146974C8D4</id><score>0.13453577</score><fulltext><json:item><extension>pdf</extension><original>true</original><mimetype>application/pdf</mimetype><uri>https://api.istex.fr/document/5B1D38C926A4F3FC8CDDF8DB627F9D146974C8D4/fulltext/pdf</uri></json:item><json:item><extension>zip</extension><original>false</original><mimetype>application/zip</mimetype><uri>https://api.istex.fr/document/5B1D38C926A4F3FC8CDDF8DB627F9D146974C8D4/fulltext/zip</uri></json:item><istex:fulltextTEI uri="https://api.istex.fr/document/5B1D38C926A4F3FC8CDDF8DB627F9D146974C8D4/fulltext/tei"><teiHeader><fileDesc><titleStmt><title level="a" type="main" xml:lang="en">The Degeneration of Dopamine Neurons in Parkinson's Disease: Insights from Embryology and Evolution of the Mesostriatocortical System</title></titleStmt><publicationStmt><authority>ISTEX</authority><publisher>Blackwell Publishing Ltd</publisher><pubPlace>Oxford, UK</pubPlace><availability><p>WILEY</p></availability><date>2004</date></publicationStmt><sourceDesc><biblStruct type="inbook"><analytic><title level="a" type="main" xml:lang="en">The Degeneration of Dopamine Neurons in Parkinson's Disease: Insights from Embryology and Evolution of the Mesostriatocortical System</title><author xml:id="author-1"><persName><forename type="first">PHILIPPE</forename><surname>VERNIER</surname></persName><email>vernier@iaf.cnrs‐gif.fr</email><affiliation>Development, Evolution, Plasticity of the Nervous System, Institute of Neurobiology A. Fessard, CNRS, 91198 Gif‐sur‐Yvette, France</affiliation></author><author xml:id="author-2"><persName><forename type="first">FREDERIC</forename><surname>MORET</surname></persName><affiliation>Development, Evolution, Plasticity of the Nervous System, Institute of Neurobiology A. Fessard, CNRS, 91198 Gif‐sur‐Yvette, France</affiliation></author><author xml:id="author-3"><persName><forename type="first">SOPHIE</forename><surname>CALLIER</surname></persName><affiliation>Development, Evolution, Plasticity of the Nervous System, Institute of Neurobiology A. Fessard, CNRS, 91198 Gif‐sur‐Yvette, France</affiliation></author><author xml:id="author-4"><persName><forename type="first">MARINA</forename><surname>SNAPYAN</surname></persName><affiliation>Development, Evolution, Plasticity of the Nervous System, Institute of Neurobiology A. Fessard, CNRS, 91198 Gif‐sur‐Yvette, France</affiliation></author><author xml:id="author-5"><persName><forename type="first">CHRISTOPHE</forename><surname>WERSINGER</surname></persName><affiliation>Department of Pediatrics, Georgetown University, Washington, District of Columbia 20007, USA</affiliation></author><author xml:id="author-6"><persName><forename type="first">ANITA</forename><surname>SIDHU</surname></persName><affiliation>Department of Pediatrics, Georgetown University, Washington, District of Columbia 20007, USA</affiliation></author></analytic><monogr><title level="j">Annals of the New York Academy of Sciences</title><idno type="pISSN">0077-8923</idno><idno type="eISSN">1749-6632</idno><idno type="DOI">10.1111/(ISSN)1749-6632</idno><imprint><publisher>Blackwell Publishing Ltd</publisher><pubPlace>Oxford, UK</pubPlace><date type="published" when="2004-12"></date><biblScope unit="volume">1035</biblScope><biblScope unit="issue">1</biblScope><biblScope unit="page" from="231">231</biblScope><biblScope unit="page" to="249">249</biblScope></imprint></monogr><idno type="istex">5B1D38C926A4F3FC8CDDF8DB627F9D146974C8D4</idno><idno type="DOI">10.1196/annals.1332.015</idno><idno type="ArticleID">NYAS231</idno></biblStruct></sourceDesc></fileDesc><profileDesc><creation><date>2004</date></creation><langUsage><language ident="en">en</language></langUsage><abstract><p>Abstract: Parkinson's disease (PD) is, to a large extent, specific to the human species. Most symptoms are the consequence of the preferential degeneration of the dopamine‐synthesizing cells of the mesostriatal‐mesocortical neuronal pathway. Reasons for that can be traced back to the evolutionary mechanisms that shaped the dopamine neurons in humans. In vertebrates, dopamine‐containing neurons and nuclei do not exhibit homogenous phenotypes. In this respect, mesencephalic dopamine neurons of the substantia nigra and ventral tegmental area are characterized by a molecular combination (tyrosine hydroxylase, aromatic amino acid decarboxylase, monoamine oxidase, vesicular monoamine transporter, dopamine transporter—to name a few), which is not found in other dopamine‐containing neurons of the vertebrate brain. In addition, the size of these mesencephalic DA nuclei is tremendously expanded in humans as compared to other vertebrates. Differentiation of the mesencephalic neurons during development depends on genetic mechanisms, which also differ from those of other dopamine nuclei. In contrast, pathophysiological approaches to PD have highlighted the role of ubiquitously expressed molecules such as a‐synuclein, parkin, and microtubule‐associated proteins. We propose that the peculiar phenotype of the dopamine mesencephalic neurons, which has been selected during vertebrate evolution and reshaped in the human lineage, has also rendered these neurons particularly prone to oxidative stress, and thus, to the fairly specific neurodegeneration of PD. Numerous evidence has been accumulated to demonstrate that perturbed regulation of DAT‐dependent dopamine uptake, DAT‐dependent accumulation of toxins, dysregulation of TH activity as well as high sensitivity of DA mesencephalic neurons to oxidants are key components of the neurodegeneration process of PD. This view points to the contribution of nonspecific mechanisms (α‐synuclein aggregation) in a highly specific cellular environment (the dopamine mesencephalic neurons) and provides a robust framework to develop novel and rational therapeutic schemes in PD.</p></abstract><textClass xml:lang="en"><keywords scheme="keyword"><list><head>keywords</head><item><term>Parkinson's disease (PD)</term></item><item><term>development</term></item><item><term>dopamine transporter</term></item><item><term>dopamine receptors</term></item><item><term>α‐synuclein</term></item><item><term>neuroprotection</term></item></list></keywords></textClass></profileDesc><revisionDesc><change when="2004-12">Published</change></revisionDesc></teiHeader></istex:fulltextTEI><json:item><extension>txt</extension><original>false</original><mimetype>text/plain</mimetype><uri>https://api.istex.fr/document/5B1D38C926A4F3FC8CDDF8DB627F9D146974C8D4/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>Blackwell Publishing Ltd</publisherName><publisherLoc>Oxford, UK</publisherLoc></publisherInfo><doi origin="wiley" registered="yes">10.1111/(ISSN)1749-6632</doi><issn type="print">0077-8923</issn><issn type="electronic">1749-6632</issn><idGroup><id type="product" value="NYAS"></id><id type="publisherDivision" value="ST"></id></idGroup><titleGroup><title type="main" sort="ANNALS OF NEW YORK ACADEMY SCIENCES">Annals of the New York Academy of Sciences</title></titleGroup></publicationMeta><publicationMeta level="part" position="12001"><doi origin="wiley">10.1111/nyas.2004.1035.issue-1</doi><titleGroup><title type="main">Protective Strategies for Neurodegenerative Diseases</title></titleGroup><numberingGroup><numbering type="journalVolume" number="1035">1035</numbering><numbering type="journalIssue">1</numbering></numberingGroup><coverDate startDate="2004-12">December 2004</coverDate></publicationMeta><publicationMeta level="unit" type="article" position="16" status="forIssue"><doi origin="wiley">10.1196/annals.1332.015</doi><idGroup><id type="unit" value="NYAS231"></id></idGroup><countGroup><count type="pageTotal" number="19"></count></countGroup><titleGroup><title type="tocHeading1">Protective Strategies for Neurodegenerative Diseases: Part VI. Parkinson's Disease</title></titleGroup><eventGroup><event type="firstOnline" date="2006-01-12"></event><event type="publishedOnlineFinalForm" date="2006-01-12"></event><event type="xmlConverted" agent="Converter:BPG_TO_WML3G version:2.3.2 mode:FullText source:FullText result:FullText" date="2010-02-27"></event><event type="xmlConverted" agent="Converter:WILEY_ML3G_TO_WILEY_ML3GV2 version:4.0.1" date="2014-03-19"></event><event type="xmlConverted" agent="Converter:WML3G_To_WML3G version:4.1.7 mode:FullText,remove_FC" date="2014-10-14"></event></eventGroup><numberingGroup><numbering type="pageFirst" number="231">231</numbering><numbering type="pageLast" number="249">249</numbering></numberingGroup><correspondenceTo>Address for correspondence: Dr. Philippe Vernier, Development, Evolution, Plasticity of the Nervous System, UPR2197, Institute of Neurobiology A. Fessard, CNRS, 91198 Gif‐sur‐Yvette, France. Voice: +33‐169‐823‐430; fax: +33‐169‐823‐447. <email normalForm="vernier@iaf.cnrs-gif.fr">vernier@iaf.cnrs‐gif.fr</email></correspondenceTo><linkGroup><link type="toTypesetVersion" href="file:NYAS.NYAS231.pdf"></link></linkGroup></publicationMeta><contentMeta><countGroup><count type="figureTotal" number="2"></count><count type="tableTotal" number="1"></count><count type="formulaTotal" number="0"></count><count type="referenceTotal" number="58"></count><count type="linksCrossRef" number="86"></count></countGroup><titleGroup><title type="main">The Degeneration of Dopamine Neurons in Parkinson's Disease: Insights from Embryology and Evolution of the Mesostriatocortical System</title></titleGroup><creators><creator creatorRole="author" xml:id="cr1" affiliationRef="#a1" corresponding="yes"><personName><givenNames>PHILIPPE</givenNames><familyName>VERNIER</familyName></personName></creator><creator creatorRole="author" xml:id="cr2" affiliationRef="#a1"><personName><givenNames>FREDERIC</givenNames><familyName>MORET</familyName></personName></creator><creator creatorRole="author" xml:id="cr3" affiliationRef="#a1"><personName><givenNames>SOPHIE</givenNames><familyName>CALLIER</familyName></personName></creator><creator creatorRole="author" xml:id="cr4" affiliationRef="#a1"><personName><givenNames>MARINA</givenNames><familyName>SNAPYAN</familyName></personName></creator><creator creatorRole="author" xml:id="cr5" affiliationRef="#a2"><personName><givenNames>CHRISTOPHE</givenNames><familyName>WERSINGER</familyName></personName></creator><creator creatorRole="author" xml:id="cr6" affiliationRef="#a2"><personName><givenNames>ANITA</givenNames><familyName>SIDHU</familyName></personName></creator></creators><affiliationGroup><affiliation xml:id="a1" countryCode="FR"><unparsedAffiliation>Development, Evolution, Plasticity of the Nervous System, Institute of Neurobiology A. Fessard, CNRS, 91198 Gif‐sur‐Yvette, France</unparsedAffiliation></affiliation><affiliation xml:id="a2" countryCode="US"><unparsedAffiliation>Department of Pediatrics, Georgetown University, Washington, District of Columbia 20007, USA</unparsedAffiliation></affiliation></affiliationGroup><keywordGroup xml:lang="en"><keyword xml:id="k1">Parkinson's disease (PD)</keyword><keyword xml:id="k2">development</keyword><keyword xml:id="k3">dopamine transporter</keyword><keyword xml:id="k4">dopamine receptors</keyword><keyword xml:id="k5">α‐synuclein</keyword><keyword xml:id="k6">neuroprotection</keyword></keywordGroup><abstractGroup><abstract type="main" xml:lang="en"><p><b>A<sc>bstract</sc>: </b> Parkinson's disease (PD) is, to a large extent, specific to the human species. Most symptoms are the consequence of the preferential degeneration of the dopamine‐synthesizing cells of the mesostriatal‐mesocortical neuronal pathway. Reasons for that can be traced back to the evolutionary mechanisms that shaped the dopamine neurons in humans. In vertebrates, dopamine‐containing neurons and nuclei do not exhibit homogenous phenotypes. In this respect, mesencephalic dopamine neurons of the substantia nigra and ventral tegmental area are characterized by a molecular combination (tyrosine hydroxylase, aromatic amino acid decarboxylase, monoamine oxidase, vesicular monoamine transporter, dopamine transporter—to name a few), which is not found in other dopamine‐containing neurons of the vertebrate brain. In addition, the size of these mesencephalic DA nuclei is tremendously expanded in humans as compared to other vertebrates. Differentiation of the mesencephalic neurons during development depends on genetic mechanisms, which also differ from those of other dopamine nuclei. In contrast, pathophysiological approaches to PD have highlighted the role of ubiquitously expressed molecules such as a‐synuclein, parkin, and microtubule‐associated proteins. We propose that the peculiar phenotype of the dopamine mesencephalic neurons, which has been selected during vertebrate evolution and reshaped in the human lineage, has also rendered these neurons particularly prone to oxidative stress, and thus, to the fairly specific neurodegeneration of PD. Numerous evidence has been accumulated to demonstrate that perturbed regulation of DAT‐dependent dopamine uptake, DAT‐dependent accumulation of toxins, dysregulation of TH activity as well as high sensitivity of DA mesencephalic neurons to oxidants are key components of the neurodegeneration process of PD. This view points to the contribution of nonspecific mechanisms (α‐synuclein aggregation) in a highly specific cellular environment (the dopamine mesencephalic neurons) and provides a robust framework to develop novel and rational therapeutic schemes in PD.</p></abstract></abstractGroup></contentMeta></header></component></istex:document></istex:metadataXml><mods version="3.6"><titleInfo lang="en"><title>The Degeneration of Dopamine Neurons in Parkinson's Disease: Insights from Embryology and Evolution of the Mesostriatocortical System</title></titleInfo><titleInfo type="alternative" contentType="CDATA" lang="en"><title>The Degeneration of Dopamine Neurons in Parkinson's Disease: Insights from Embryology and Evolution of the Mesostriatocortical System</title></titleInfo><name type="personal"><namePart type="given">PHILIPPE</namePart><namePart type="family">VERNIER</namePart><affiliation>Development, Evolution, Plasticity of the Nervous System, Institute of Neurobiology A. Fessard, CNRS, 91198 Gif‐sur‐Yvette, France</affiliation><affiliation>E-mail: vernier@iaf.cnrs‐gif.fr</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">FREDERIC</namePart><namePart type="family">MORET</namePart><affiliation>Development, Evolution, Plasticity of the Nervous System, Institute of Neurobiology A. Fessard, CNRS, 91198 Gif‐sur‐Yvette, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">SOPHIE</namePart><namePart type="family">CALLIER</namePart><affiliation>Development, Evolution, Plasticity of the Nervous System, Institute of Neurobiology A. Fessard, CNRS, 91198 Gif‐sur‐Yvette, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">MARINA</namePart><namePart type="family">SNAPYAN</namePart><affiliation>Development, Evolution, Plasticity of the Nervous System, Institute of Neurobiology A. Fessard, CNRS, 91198 Gif‐sur‐Yvette, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">CHRISTOPHE</namePart><namePart type="family">WERSINGER</namePart><affiliation>Department of Pediatrics, Georgetown University, Washington, District of Columbia 20007, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">ANITA</namePart><namePart type="family">SIDHU</namePart><affiliation>Department of Pediatrics, Georgetown University, Washington, District of Columbia 20007, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="article" displayLabel="article"></genre><originInfo><publisher>Blackwell Publishing Ltd</publisher><place><placeTerm type="text">Oxford, UK</placeTerm></place><dateIssued encoding="w3cdtf">2004-12</dateIssued><copyrightDate encoding="w3cdtf">2004</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">58</extent></physicalDescription><abstract>Abstract: Parkinson's disease (PD) is, to a large extent, specific to the human species. Most symptoms are the consequence of the preferential degeneration of the dopamine‐synthesizing cells of the mesostriatal‐mesocortical neuronal pathway. Reasons for that can be traced back to the evolutionary mechanisms that shaped the dopamine neurons in humans. In vertebrates, dopamine‐containing neurons and nuclei do not exhibit homogenous phenotypes. In this respect, mesencephalic dopamine neurons of the substantia nigra and ventral tegmental area are characterized by a molecular combination (tyrosine hydroxylase, aromatic amino acid decarboxylase, monoamine oxidase, vesicular monoamine transporter, dopamine transporter—to name a few), which is not found in other dopamine‐containing neurons of the vertebrate brain. In addition, the size of these mesencephalic DA nuclei is tremendously expanded in humans as compared to other vertebrates. Differentiation of the mesencephalic neurons during development depends on genetic mechanisms, which also differ from those of other dopamine nuclei. In contrast, pathophysiological approaches to PD have highlighted the role of ubiquitously expressed molecules such as a‐synuclein, parkin, and microtubule‐associated proteins. We propose that the peculiar phenotype of the dopamine mesencephalic neurons, which has been selected during vertebrate evolution and reshaped in the human lineage, has also rendered these neurons particularly prone to oxidative stress, and thus, to the fairly specific neurodegeneration of PD. Numerous evidence has been accumulated to demonstrate that perturbed regulation of DAT‐dependent dopamine uptake, DAT‐dependent accumulation of toxins, dysregulation of TH activity as well as high sensitivity of DA mesencephalic neurons to oxidants are key components of the neurodegeneration process of PD. This view points to the contribution of nonspecific mechanisms (α‐synuclein aggregation) in a highly specific cellular environment (the dopamine mesencephalic neurons) and provides a robust framework to develop novel and rational therapeutic schemes in PD.</abstract><subject lang="en"><genre>keywords</genre><topic>Parkinson's disease (PD)</topic><topic>development</topic><topic>dopamine transporter</topic><topic>dopamine receptors</topic><topic>α‐synuclein</topic><topic>neuroprotection</topic></subject><relatedItem type="host"><titleInfo><title>Annals of the New York Academy of Sciences</title></titleInfo><genre type="journal">journal</genre><identifier type="ISSN">0077-8923</identifier><identifier type="eISSN">1749-6632</identifier><identifier type="DOI">10.1111/(ISSN)1749-6632</identifier><identifier type="PublisherID">NYAS</identifier><part><date>2004</date><detail type="title"><title>Protective Strategies for Neurodegenerative Diseases</title></detail><detail type="volume"><caption>vol.</caption><number>1035</number></detail><detail type="issue"><caption>no.</caption><number>1</number></detail><extent unit="pages"><start>231</start><end>249</end><total>19</total></extent></part></relatedItem><identifier type="istex">5B1D38C926A4F3FC8CDDF8DB627F9D146974C8D4</identifier><identifier type="DOI">10.1196/annals.1332.015</identifier><identifier type="ArticleID">NYAS231</identifier><recordInfo><recordContentSource>WILEY</recordContentSource><recordOrigin>Blackwell Publishing Ltd</recordOrigin></recordInfo></mods></metadata><serie></serie></istex></record>Pour manipuler ce document sous Unix (Dilib)
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