Oxidative mechanisms in nigral cell death in Parkinson's disease.
Identifieur interne : 004446 ( PubMed/Corpus ); précédent : 004445; suivant : 004447Oxidative mechanisms in nigral cell death in Parkinson's disease.
Auteurs : P. JennerSource :
- Movement disorders : official journal of the Movement Disorder Society [ 0885-3185 ] ; 1998.
English descriptors
- KwdEn :
- Animals, Cell Death (physiology), Cytochrome P-450 Enzyme System (physiology), Disease Models, Animal, Free Radicals, Humans, Lipid Peroxidation (physiology), Mice, Nitric Oxide (physiology), Parkinson Disease (pathology), Parkinson Disease (physiopathology), Reactive Oxygen Species (metabolism), Substantia Nigra (pathology), Substantia Nigra (physiopathology).
- MESH :
- chemical , metabolism : Reactive Oxygen Species.
- chemical , physiology : Cytochrome P-450 Enzyme System, Nitric Oxide.
- pathology : Parkinson Disease, Substantia Nigra.
- physiology : Cell Death, Lipid Peroxidation.
- physiopathology : Parkinson Disease, Substantia Nigra.
- Animals, Disease Models, Animal, Free Radicals, Humans, Mice.
Abstract
Oxidative stress may contribute to nigral cell death in Parkinson's disease based on postmortem investigations showing increased iron levels, decreased levels of reduced glutathione (GSH), and impaired mitochondrial function. This leads to oxidative damage because lipid peroxidation is increased in substantia nigra and there is a widespread increase in protein and DNA oxidation in the brain in Parkinson's disease. Nitric oxide (NO) may be one of the free radical species involved in nigral degeneration. NO is involved in the production of hydroxyl radicals resulting from MPP+-induced dopamine efflux in striatum. Mice treated with the neuronal nitric oxide synthase (NOS) inhibitor 7-nitroindazole show reduced toxicity to MPTP and knock-out mice lacking neuronal NOS show decreased MPTP susceptibility. In primates, 7-nitroindazole inhibits MPTP toxicity but this remains controversial because no protection is afforded by the nonspecific NOS inhibitor, L-NAME. Indeed, in Parkinson's disease itself, there is little evidence for nitric oxide's involvement in nigral pathology. A susceptibility factor for the development of Parkinson's disease may involve isoforms of cytochrome P450, some of which are found in the brain. CYP2EI, which is associated with free radical production and the formation of endogenous toxins, is selectively localized in nigral dopamine-containing cells. CYP2E1 metabolizes n-hexane leading to the formation of its neurotoxic metabolite 2,5-hexanedione which may explain cases of solvent-induced parkinsonism. Oxidative processes clearly contribute to the pathology of Parkinson's disease but are probably secondary to some other primary unidentified cause, presumably genetic or environmental. Nevertheless, their involvement may allow therapeutic intervention in the cascade of events associated with the progression of Parkinson's disease.
PubMed: 9613715
Links to Exploration step
pubmed:9613715Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Oxidative mechanisms in nigral cell death in Parkinson's disease.</title>
<author><name sortKey="Jenner, P" sort="Jenner, P" uniqKey="Jenner P" first="P" last="Jenner">P. Jenner</name>
<affiliation><nlm:affiliation>Neurodegenerative Disease Research Centre, Biomedical Science Division, London, United Kingdom.</nlm:affiliation>
</affiliation>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">PubMed</idno>
<date when="1998">1998</date>
<idno type="RBID">pubmed:9613715</idno>
<idno type="pmid">9613715</idno>
<idno type="wicri:Area/PubMed/Corpus">004446</idno>
</publicationStmt>
<sourceDesc><biblStruct><analytic><title xml:lang="en">Oxidative mechanisms in nigral cell death in Parkinson's disease.</title>
<author><name sortKey="Jenner, P" sort="Jenner, P" uniqKey="Jenner P" first="P" last="Jenner">P. Jenner</name>
<affiliation><nlm:affiliation>Neurodegenerative Disease Research Centre, Biomedical Science Division, London, United Kingdom.</nlm:affiliation>
</affiliation>
</author>
</analytic>
<series><title level="j">Movement disorders : official journal of the Movement Disorder Society</title>
<idno type="ISSN">0885-3185</idno>
<imprint><date when="1998" type="published">1998</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term>
<term>Cell Death (physiology)</term>
<term>Cytochrome P-450 Enzyme System (physiology)</term>
<term>Disease Models, Animal</term>
<term>Free Radicals</term>
<term>Humans</term>
<term>Lipid Peroxidation (physiology)</term>
<term>Mice</term>
<term>Nitric Oxide (physiology)</term>
<term>Parkinson Disease (pathology)</term>
<term>Parkinson Disease (physiopathology)</term>
<term>Reactive Oxygen Species (metabolism)</term>
<term>Substantia Nigra (pathology)</term>
<term>Substantia Nigra (physiopathology)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Reactive Oxygen Species</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="physiology" xml:lang="en"><term>Cytochrome P-450 Enzyme System</term>
<term>Nitric Oxide</term>
</keywords>
<keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Parkinson Disease</term>
<term>Substantia Nigra</term>
</keywords>
<keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>Cell Death</term>
<term>Lipid Peroxidation</term>
</keywords>
<keywords scheme="MESH" qualifier="physiopathology" xml:lang="en"><term>Parkinson Disease</term>
<term>Substantia Nigra</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Animals</term>
<term>Disease Models, Animal</term>
<term>Free Radicals</term>
<term>Humans</term>
<term>Mice</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en">Oxidative stress may contribute to nigral cell death in Parkinson's disease based on postmortem investigations showing increased iron levels, decreased levels of reduced glutathione (GSH), and impaired mitochondrial function. This leads to oxidative damage because lipid peroxidation is increased in substantia nigra and there is a widespread increase in protein and DNA oxidation in the brain in Parkinson's disease. Nitric oxide (NO) may be one of the free radical species involved in nigral degeneration. NO is involved in the production of hydroxyl radicals resulting from MPP+-induced dopamine efflux in striatum. Mice treated with the neuronal nitric oxide synthase (NOS) inhibitor 7-nitroindazole show reduced toxicity to MPTP and knock-out mice lacking neuronal NOS show decreased MPTP susceptibility. In primates, 7-nitroindazole inhibits MPTP toxicity but this remains controversial because no protection is afforded by the nonspecific NOS inhibitor, L-NAME. Indeed, in Parkinson's disease itself, there is little evidence for nitric oxide's involvement in nigral pathology. A susceptibility factor for the development of Parkinson's disease may involve isoforms of cytochrome P450, some of which are found in the brain. CYP2EI, which is associated with free radical production and the formation of endogenous toxins, is selectively localized in nigral dopamine-containing cells. CYP2E1 metabolizes n-hexane leading to the formation of its neurotoxic metabolite 2,5-hexanedione which may explain cases of solvent-induced parkinsonism. Oxidative processes clearly contribute to the pathology of Parkinson's disease but are probably secondary to some other primary unidentified cause, presumably genetic or environmental. Nevertheless, their involvement may allow therapeutic intervention in the cascade of events associated with the progression of Parkinson's disease.</div>
</front>
</TEI>
<pubmed><MedlineCitation Owner="NLM" Status="MEDLINE"><PMID Version="1">9613715</PMID>
<DateCreated><Year>1998</Year>
<Month>08</Month>
<Day>06</Day>
</DateCreated>
<DateCompleted><Year>1998</Year>
<Month>08</Month>
<Day>06</Day>
</DateCompleted>
<DateRevised><Year>2013</Year>
<Month>11</Month>
<Day>21</Day>
</DateRevised>
<Article PubModel="Print"><Journal><ISSN IssnType="Print">0885-3185</ISSN>
<JournalIssue CitedMedium="Print"><Volume>13 Suppl 1</Volume>
<PubDate><Year>1998</Year>
</PubDate>
</JournalIssue>
<Title>Movement disorders : official journal of the Movement Disorder Society</Title>
<ISOAbbreviation>Mov. Disord.</ISOAbbreviation>
</Journal>
<ArticleTitle>Oxidative mechanisms in nigral cell death in Parkinson's disease.</ArticleTitle>
<Pagination><MedlinePgn>24-34</MedlinePgn>
</Pagination>
<Abstract><AbstractText>Oxidative stress may contribute to nigral cell death in Parkinson's disease based on postmortem investigations showing increased iron levels, decreased levels of reduced glutathione (GSH), and impaired mitochondrial function. This leads to oxidative damage because lipid peroxidation is increased in substantia nigra and there is a widespread increase in protein and DNA oxidation in the brain in Parkinson's disease. Nitric oxide (NO) may be one of the free radical species involved in nigral degeneration. NO is involved in the production of hydroxyl radicals resulting from MPP+-induced dopamine efflux in striatum. Mice treated with the neuronal nitric oxide synthase (NOS) inhibitor 7-nitroindazole show reduced toxicity to MPTP and knock-out mice lacking neuronal NOS show decreased MPTP susceptibility. In primates, 7-nitroindazole inhibits MPTP toxicity but this remains controversial because no protection is afforded by the nonspecific NOS inhibitor, L-NAME. Indeed, in Parkinson's disease itself, there is little evidence for nitric oxide's involvement in nigral pathology. A susceptibility factor for the development of Parkinson's disease may involve isoforms of cytochrome P450, some of which are found in the brain. CYP2EI, which is associated with free radical production and the formation of endogenous toxins, is selectively localized in nigral dopamine-containing cells. CYP2E1 metabolizes n-hexane leading to the formation of its neurotoxic metabolite 2,5-hexanedione which may explain cases of solvent-induced parkinsonism. Oxidative processes clearly contribute to the pathology of Parkinson's disease but are probably secondary to some other primary unidentified cause, presumably genetic or environmental. Nevertheless, their involvement may allow therapeutic intervention in the cascade of events associated with the progression of Parkinson's disease.</AbstractText>
</Abstract>
<AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Jenner</LastName>
<ForeName>P</ForeName>
<Initials>P</Initials>
<AffiliationInfo><Affiliation>Neurodegenerative Disease Research Centre, Biomedical Science Division, London, United Kingdom.</Affiliation>
</AffiliationInfo>
</Author>
</AuthorList>
<Language>eng</Language>
<GrantList CompleteYN="Y"><Grant><Agency>Wellcome Trust</Agency>
<Country>United Kingdom</Country>
</Grant>
</GrantList>
<PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType>
<PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType>
<PublicationType UI="D016454">Review</PublicationType>
</PublicationTypeList>
</Article>
<MedlineJournalInfo><Country>UNITED STATES</Country>
<MedlineTA>Mov Disord</MedlineTA>
<NlmUniqueID>8610688</NlmUniqueID>
<ISSNLinking>0885-3185</ISSNLinking>
</MedlineJournalInfo>
<ChemicalList><Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D005609">Free Radicals</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D017382">Reactive Oxygen Species</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>31C4KY9ESH</RegistryNumber>
<NameOfSubstance UI="D009569">Nitric Oxide</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>9035-51-2</RegistryNumber>
<NameOfSubstance UI="D003577">Cytochrome P-450 Enzyme System</NameOfSubstance>
</Chemical>
</ChemicalList>
<CitationSubset>IM</CitationSubset>
<MeshHeadingList><MeshHeading><DescriptorName MajorTopicYN="N" UI="D000818">Animals</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName MajorTopicYN="N" UI="D016923">Cell Death</DescriptorName>
<QualifierName MajorTopicYN="Y" UI="Q000502">physiology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName MajorTopicYN="N" UI="D003577">Cytochrome P-450 Enzyme System</DescriptorName>
<QualifierName MajorTopicYN="N" UI="Q000502">physiology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName MajorTopicYN="N" UI="D004195">Disease Models, Animal</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName MajorTopicYN="N" UI="D005609">Free Radicals</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName MajorTopicYN="N" UI="D006801">Humans</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName MajorTopicYN="N" UI="D015227">Lipid Peroxidation</DescriptorName>
<QualifierName MajorTopicYN="Y" UI="Q000502">physiology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName MajorTopicYN="N" UI="D051379">Mice</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName MajorTopicYN="N" UI="D009569">Nitric Oxide</DescriptorName>
<QualifierName MajorTopicYN="N" UI="Q000502">physiology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName MajorTopicYN="N" UI="D010300">Parkinson Disease</DescriptorName>
<QualifierName MajorTopicYN="N" UI="Q000473">pathology</QualifierName>
<QualifierName MajorTopicYN="Y" UI="Q000503">physiopathology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName MajorTopicYN="N" UI="D017382">Reactive Oxygen Species</DescriptorName>
<QualifierName MajorTopicYN="Y" UI="Q000378">metabolism</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName MajorTopicYN="N" UI="D013378">Substantia Nigra</DescriptorName>
<QualifierName MajorTopicYN="N" UI="Q000473">pathology</QualifierName>
<QualifierName MajorTopicYN="Y" UI="Q000503">physiopathology</QualifierName>
</MeshHeading>
</MeshHeadingList>
<NumberOfReferences>100</NumberOfReferences>
</MedlineCitation>
<PubmedData><History><PubMedPubDate PubStatus="pubmed"><Year>1998</Year>
<Month>6</Month>
<Day>5</Day>
</PubMedPubDate>
<PubMedPubDate PubStatus="medline"><Year>1998</Year>
<Month>6</Month>
<Day>5</Day>
<Hour>0</Hour>
<Minute>1</Minute>
</PubMedPubDate>
<PubMedPubDate PubStatus="entrez"><Year>1998</Year>
<Month>6</Month>
<Day>5</Day>
<Hour>0</Hour>
<Minute>0</Minute>
</PubMedPubDate>
</History>
<PublicationStatus>ppublish</PublicationStatus>
<ArticleIdList><ArticleId IdType="pubmed">9613715</ArticleId>
</ArticleIdList>
</PubmedData>
</pubmed>
</record>
Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Wicri/Santé/explor/MovDisordV3/Data/PubMed/Corpus
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 004446 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/PubMed/Corpus/biblio.hfd -nk 004446 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien |wiki= Wicri/Santé |area= MovDisordV3 |flux= PubMed |étape= Corpus |type= RBID |clé= pubmed:9613715 |texte= Oxidative mechanisms in nigral cell death in Parkinson's disease. }}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/PubMed/Corpus/RBID.i -Sk "pubmed:9613715" \ | HfdSelect -Kh $EXPLOR_AREA/Data/PubMed/Corpus/biblio.hfd \ | NlmPubMed2Wicri -a MovDisordV3
![]() | This area was generated with Dilib version V0.6.23. | ![]() |