Mechanism and consequences of nerve cell death in Parkinson's disease.
Identifieur interne : 001271 ( PubMed/Checkpoint ); précédent : 001270; suivant : 001272Mechanism and consequences of nerve cell death in Parkinson's disease.
Auteurs : E C Hirsch [France]Source :
- Journal of neural transmission. Supplementum [ 0303-6995 ] ; 1999.
English descriptors
- KwdEn :
- MESH :
- pathology : Neurons, Parkinson Disease.
- physiology : Cell Death.
- Animals, Humans.
Abstract
The etiology of Parkinson's disease remains unknown, making it difficult to develop therapeutical approaches to stop the progression of the disease. The best known treatment to date is based on the use of L-DOPA or dopaminergic agonists. These are merely substitutive therapies and have limitations because of their side effects. Thus, the development of new therapeutical strategies will require a far better knowledge of the mechanism and the consequences of nerve cell death in Parkinson's disease. Parkinson's disease is characterized by a selective vulnerability of sub-populations of dopaminergic neurons in the mesencephalon. The fact that the neurons which degenerate in Parkinson's disease are already sensitive to oxidative stress in control subjects and the reported increased production of oxygen free radicals in Parkinson's disease suggest that oxidative stress may be involved in the mechanism of nerve cell death. Furthermore, oxygen free radicals are also involved in an oxygen-dependent pro-apoptotic pathway stimulated by the inflammatory reaction observed in Parkinson's disease. These data suggest that anti-oxidant or anti-inflammatory treatments may slow down the progression of the disease. On the other hand, new substitutive therapies may be developed by trying to restore the activity of the neurons located downstream from the nigrostriatal pathway. Indeed, the nigrostriatal denervation induces a hyper-activity of the output structures of the basal ganglia (internal segment of the globus pallidus and substantia nigra pars reticulata), as demonstrated in various animal models of the disease. These changes in the activity of the output structures of the basal ganglia seem to be directly induced by the hyperactivity of the glutamatergic afferent fibers from the subthalamic nucleus. The fact that L-DOPA treatment or a reduction in the activity of the subthalamic nucleus alleviate the symptoms of the disease and restore the activity of the output structures of the basal ganglia in parkinsonism suggests that these structures play a key role in the pathophysiology of the disease and could represent a potential therapeutic target.
PubMed: 10370907
Affiliations:
Links toward previous steps (curation, corpus...)
Links to Exploration step
pubmed:10370907Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Mechanism and consequences of nerve cell death in Parkinson's disease.</title><author><name sortKey="Hirsch, E C" sort="Hirsch, E C" uniqKey="Hirsch E" first="E C" last="Hirsch">E C Hirsch</name><affiliation wicri:level="3"><nlm:affiliation>INSERM U 289, Hôpital de la Salpêtrière, Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>INSERM U 289, Hôpital de la Salpêtrière, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="1999">1999</date><idno type="RBID">pubmed:10370907</idno><idno type="pmid">10370907</idno><idno type="wicri:Area/PubMed/Corpus">001433</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">001433</idno><idno type="wicri:Area/PubMed/Curation">001392</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">001392</idno><idno type="wicri:Area/PubMed/Checkpoint">001392</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">001392</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Mechanism and consequences of nerve cell death in Parkinson's disease.</title><author><name sortKey="Hirsch, E C" sort="Hirsch, E C" uniqKey="Hirsch E" first="E C" last="Hirsch">E C Hirsch</name><affiliation wicri:level="3"><nlm:affiliation>INSERM U 289, Hôpital de la Salpêtrière, Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>INSERM U 289, Hôpital de la Salpêtrière, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author></analytic><series><title level="j">Journal of neural transmission. Supplementum</title><idno type="ISSN">0303-6995</idno><imprint><date when="1999" type="published">1999</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Cell Death (physiology)</term><term>Humans</term><term>Neurons (pathology)</term><term>Parkinson Disease (pathology)</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Neurons</term><term>Parkinson Disease</term></keywords><keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>Cell Death</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Humans</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The etiology of Parkinson's disease remains unknown, making it difficult to develop therapeutical approaches to stop the progression of the disease. The best known treatment to date is based on the use of L-DOPA or dopaminergic agonists. These are merely substitutive therapies and have limitations because of their side effects. Thus, the development of new therapeutical strategies will require a far better knowledge of the mechanism and the consequences of nerve cell death in Parkinson's disease. Parkinson's disease is characterized by a selective vulnerability of sub-populations of dopaminergic neurons in the mesencephalon. The fact that the neurons which degenerate in Parkinson's disease are already sensitive to oxidative stress in control subjects and the reported increased production of oxygen free radicals in Parkinson's disease suggest that oxidative stress may be involved in the mechanism of nerve cell death. Furthermore, oxygen free radicals are also involved in an oxygen-dependent pro-apoptotic pathway stimulated by the inflammatory reaction observed in Parkinson's disease. These data suggest that anti-oxidant or anti-inflammatory treatments may slow down the progression of the disease. On the other hand, new substitutive therapies may be developed by trying to restore the activity of the neurons located downstream from the nigrostriatal pathway. Indeed, the nigrostriatal denervation induces a hyper-activity of the output structures of the basal ganglia (internal segment of the globus pallidus and substantia nigra pars reticulata), as demonstrated in various animal models of the disease. These changes in the activity of the output structures of the basal ganglia seem to be directly induced by the hyperactivity of the glutamatergic afferent fibers from the subthalamic nucleus. The fact that L-DOPA treatment or a reduction in the activity of the subthalamic nucleus alleviate the symptoms of the disease and restore the activity of the output structures of the basal ganglia in parkinsonism suggests that these structures play a key role in the pathophysiology of the disease and could represent a potential therapeutic target.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">10370907</PMID><DateCreated><Year>1999</Year><Month>08</Month><Day>02</Day></DateCreated><DateCompleted><Year>1999</Year><Month>08</Month><Day>02</Day></DateCompleted><DateRevised><Year>2005</Year><Month>11</Month><Day>16</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Print">0303-6995</ISSN><JournalIssue CitedMedium="Print"><Volume>56</Volume><PubDate><Year>1999</Year></PubDate></JournalIssue><Title>Journal of neural transmission. Supplementum</Title><ISOAbbreviation>J. Neural Transm. Suppl.</ISOAbbreviation></Journal><ArticleTitle>Mechanism and consequences of nerve cell death in Parkinson's disease.</ArticleTitle><Pagination><MedlinePgn>127-37</MedlinePgn></Pagination><Abstract><AbstractText>The etiology of Parkinson's disease remains unknown, making it difficult to develop therapeutical approaches to stop the progression of the disease. The best known treatment to date is based on the use of L-DOPA or dopaminergic agonists. These are merely substitutive therapies and have limitations because of their side effects. Thus, the development of new therapeutical strategies will require a far better knowledge of the mechanism and the consequences of nerve cell death in Parkinson's disease. Parkinson's disease is characterized by a selective vulnerability of sub-populations of dopaminergic neurons in the mesencephalon. The fact that the neurons which degenerate in Parkinson's disease are already sensitive to oxidative stress in control subjects and the reported increased production of oxygen free radicals in Parkinson's disease suggest that oxidative stress may be involved in the mechanism of nerve cell death. Furthermore, oxygen free radicals are also involved in an oxygen-dependent pro-apoptotic pathway stimulated by the inflammatory reaction observed in Parkinson's disease. These data suggest that anti-oxidant or anti-inflammatory treatments may slow down the progression of the disease. On the other hand, new substitutive therapies may be developed by trying to restore the activity of the neurons located downstream from the nigrostriatal pathway. Indeed, the nigrostriatal denervation induces a hyper-activity of the output structures of the basal ganglia (internal segment of the globus pallidus and substantia nigra pars reticulata), as demonstrated in various animal models of the disease. These changes in the activity of the output structures of the basal ganglia seem to be directly induced by the hyperactivity of the glutamatergic afferent fibers from the subthalamic nucleus. The fact that L-DOPA treatment or a reduction in the activity of the subthalamic nucleus alleviate the symptoms of the disease and restore the activity of the output structures of the basal ganglia in parkinsonism suggests that these structures play a key role in the pathophysiology of the disease and could represent a potential therapeutic target.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Hirsch</LastName><ForeName>E C</ForeName><Initials>EC</Initials><AffiliationInfo><Affiliation>INSERM U 289, Hôpital de la Salpêtrière, Paris, France.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D016454">Review</PublicationType></PublicationTypeList></Article><MedlineJournalInfo><Country>Austria</Country><MedlineTA>J Neural Transm Suppl</MedlineTA><NlmUniqueID>0425126</NlmUniqueID><ISSNLinking>0303-6995</ISSNLinking></MedlineJournalInfo><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D016923" MajorTopicYN="N">Cell Death</DescriptorName><QualifierName UI="Q000502" MajorTopicYN="N">physiology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D009474" MajorTopicYN="N">Neurons</DescriptorName><QualifierName UI="Q000473" MajorTopicYN="Y">pathology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D010300" MajorTopicYN="N">Parkinson Disease</DescriptorName><QualifierName UI="Q000473" MajorTopicYN="Y">pathology</QualifierName></MeshHeading></MeshHeadingList><NumberOfReferences>60</NumberOfReferences></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="pubmed"><Year>1999</Year><Month>6</Month><Day>17</Day></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>1999</Year><Month>6</Month><Day>17</Day><Hour>0</Hour><Minute>1</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>1999</Year><Month>6</Month><Day>17</Day><Hour>0</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">10370907</ArticleId></ArticleIdList></PubmedData></pubmed><affiliations><list><country><li>France</li></country><region><li>Île-de-France</li></region><settlement><li>Paris</li></settlement></list><tree><country name="France"><region name="Île-de-France"><name sortKey="Hirsch, E C" sort="Hirsch, E C" uniqKey="Hirsch E" first="E C" last="Hirsch">E C Hirsch</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Wicri/Sante/explor/ParkinsonFranceV1/Data/PubMed/Checkpoint
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 001271 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/PubMed/Checkpoint/biblio.hfd -nk 001271 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Wicri/Sante
|area= ParkinsonFranceV1
|flux= PubMed
|étape= Checkpoint
|type= RBID
|clé= pubmed:10370907
|texte= Mechanism and consequences of nerve cell death in Parkinson's disease.
}}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/PubMed/Checkpoint/RBID.i -Sk "pubmed:10370907" \
| HfdSelect -Kh $EXPLOR_AREA/Data/PubMed/Checkpoint/biblio.hfd \
| NlmPubMed2Wicri -a ParkinsonFranceV1
| This area was generated with Dilib version V0.6.29. |  |