File Download

There are no files associated with this item.

  Links for fulltext
     (May Require Subscription)
Supplementary

Article: Hypersensitivity of DJ-1-deficient mice to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyrindine (MPTP) and oxidative stress

TitleHypersensitivity of DJ-1-deficient mice to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyrindine (MPTP) and oxidative stress
Authors
Issue Date2005
Citation
Proceedings of the National Academy of Sciences of the United States of America, 2005, v. 102, n. 14, p. 5215-5220 How to Cite?
AbstractMutations of the DJ-1 (PARK7) gene are linked to familial Parkinson's disease. We used gene targeting to generate DJ-1-deficient mice that were viable, fertile, and showed no gross anatomical or neuronal abnormalities. Dopaminergic neuron numbers in the substantia nigra and fiber densities and dopamine levels in the striatum were normal. However, DJ-1-/- mice showed hypolocomotion when subjected to amphetamine challenge and increased striatal denervation and dopaminergic neuron loss induced by 1-methyl-4-phenyl-1,2,3,6- tetrahydropyrindine. DJ-1-/- embryonic cortical neurons showed increased sensitivity to oxidative, but not nonoxidative, insults. Restoration of DJ-1 expression to DJ-1-/- mice or cells via adenoviral vector delivery mitigated all phenotypes. WT mice that received adenoviral delivery of DJ-1 resisted 1-methyl-4-phenyl-1,2,3,6-tetrahydropyrindine-induced striatal damage, and neurons overexpressing DJ-1 were protected from oxidative stress in vitro. Thus, DJ-1 protects against neuronal oxidative stress, and loss of DJ-1 may lead to Parkinson's disease by conferring hypersensitivity to dopaminergic insults. © 2005 by The National Academy of Sciences of the USA.
Persistent Identifierhttp://hdl.handle.net/10722/292534
ISSN
2023 Impact Factor: 9.4
2023 SCImago Journal Rankings: 3.737
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorKim, Raymond H.-
dc.contributor.authorSmith, Patrice D.-
dc.contributor.authorAleyasin, Hossein-
dc.contributor.authorHayley, Shawn-
dc.contributor.authorMount, Matthew P.-
dc.contributor.authorPownall, Scott-
dc.contributor.authorWakeham, Andrew-
dc.contributor.authorYou-Ten, Annick J.-
dc.contributor.authorKalia, Suneil K.-
dc.contributor.authorHorne, Patrick-
dc.contributor.authorWestaway, David-
dc.contributor.authorLozano, Andres M.-
dc.contributor.authorAnisman, Hymie-
dc.contributor.authorPark, David S.-
dc.contributor.authorMak, Tak W.-
dc.date.accessioned2020-11-17T14:56:41Z-
dc.date.available2020-11-17T14:56:41Z-
dc.date.issued2005-
dc.identifier.citationProceedings of the National Academy of Sciences of the United States of America, 2005, v. 102, n. 14, p. 5215-5220-
dc.identifier.issn0027-8424-
dc.identifier.urihttp://hdl.handle.net/10722/292534-
dc.description.abstractMutations of the DJ-1 (PARK7) gene are linked to familial Parkinson's disease. We used gene targeting to generate DJ-1-deficient mice that were viable, fertile, and showed no gross anatomical or neuronal abnormalities. Dopaminergic neuron numbers in the substantia nigra and fiber densities and dopamine levels in the striatum were normal. However, DJ-1-/- mice showed hypolocomotion when subjected to amphetamine challenge and increased striatal denervation and dopaminergic neuron loss induced by 1-methyl-4-phenyl-1,2,3,6- tetrahydropyrindine. DJ-1-/- embryonic cortical neurons showed increased sensitivity to oxidative, but not nonoxidative, insults. Restoration of DJ-1 expression to DJ-1-/- mice or cells via adenoviral vector delivery mitigated all phenotypes. WT mice that received adenoviral delivery of DJ-1 resisted 1-methyl-4-phenyl-1,2,3,6-tetrahydropyrindine-induced striatal damage, and neurons overexpressing DJ-1 were protected from oxidative stress in vitro. Thus, DJ-1 protects against neuronal oxidative stress, and loss of DJ-1 may lead to Parkinson's disease by conferring hypersensitivity to dopaminergic insults. © 2005 by The National Academy of Sciences of the USA.-
dc.languageeng-
dc.relation.ispartofProceedings of the National Academy of Sciences of the United States of America-
dc.titleHypersensitivity of DJ-1-deficient mice to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyrindine (MPTP) and oxidative stress-
dc.typeArticle-
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1073/pnas.0501282102-
dc.identifier.pmid15784737-
dc.identifier.pmcidPMC555037-
dc.identifier.scopuseid_2-s2.0-20144389422-
dc.identifier.volume102-
dc.identifier.issue14-
dc.identifier.spage5215-
dc.identifier.epage5220-
dc.identifier.isiWOS:000228195800053-
dc.identifier.issnl0027-8424-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats