{"@context":{"@vocab":"https://cir.nii.ac.jp/schema/1.0/","rdfs":"http://www.w3.org/2000/01/rdf-schema#","dc":"http://purl.org/dc/elements/1.1/","dcterms":"http://purl.org/dc/terms/","foaf":"http://xmlns.com/foaf/0.1/","prism":"http://prismstandard.org/namespaces/basic/2.0/","cinii":"http://ci.nii.ac.jp/ns/1.0/","datacite":"https://schema.datacite.org/meta/kernel-4/","ndl":"http://ndl.go.jp/dcndl/terms/","jpcoar":"https://github.com/JPCOAR/schema/blob/master/2.0/"},"@id":"https://cir.nii.ac.jp/crid/1360846644337652352.json","@type":"Article","productIdentifier":[{"identifier":{"@type":"DOI","@value":"10.1371/journal.pone.0029935"}},{"identifier":{"@type":"URI","@value":"http://dx.plos.org/10.1371/journal.pone.0029935"}},{"identifier":{"@type":"PMID","@value":"22253830"}}],"resourceType":"学術雑誌論文(journal article)","dc:title":[{"@value":"Apoptosis Signal-Regulating Kinase 1 Mediates MPTP Toxicity and Regulates Glial Activation"}],"description":[{"notation":[{"@value":"Apoptosis signal-regulating kinase 1 (ASK1), a member of the mitogen-activated protein kinase 3 family, is activated by oxidative stress. The death-signaling pathway mediated by ASK1 is inhibited by DJ-1, which is linked to recessively inherited Parkinson's disease (PD). Considering that DJ-1 deficiency exacerbates the toxicity of the mitochondrial complex I inhibitor 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), we sought to investigate the direct role and mechanism of ASK1 in MPTP-induced dopamine neuron toxicity. In the present study, we found that MPTP administration to wild-type mice activates ASK1 in the midbrain. In ASK1 null mice, MPTP-induced motor impairment was less profound, and striatal dopamine content and nigral dopamine neuron counts were relatively preserved compared to wild-type littermates. Further, microglia and astrocyte activation seen in wild-type mice challenged with MPTP was markedly attenuated in ASK⁻/⁻ mice. These data suggest that ASK1 is a key player in MPTP-induced glial activation linking oxidative stress with neuroinflammation, two well recognized pathogenetic factors in PD. These findings demonstrate that ASK1 is an important effector of MPTP-induced toxicity and suggest that inhibiting this kinase is a plausible therapeutic strategy for protecting dopamine neurons in PD."}]}],"creator":[{"@id":"https://cir.nii.ac.jp/crid/1380284922742728072","@type":"Researcher","foaf:name":[{"@value":"Kang-Woo Lee"}]},{"@id":"https://cir.nii.ac.jp/crid/1380284922742728069","@type":"Researcher","foaf:name":[{"@value":"Xin Zhao"}]},{"@id":"https://cir.nii.ac.jp/crid/1380284922742728071","@type":"Researcher","foaf:name":[{"@value":"Joo-Young Im"}]},{"@id":"https://cir.nii.ac.jp/crid/1380284922742728066","@type":"Researcher","foaf:name":[{"@value":"Hilary Grosso"}]},{"@id":"https://cir.nii.ac.jp/crid/1380284922742728064","@type":"Researcher","foaf:name":[{"@value":"Won Hee Jang"}]},{"@id":"https://cir.nii.ac.jp/crid/1380284922742728070","@type":"Researcher","foaf:name":[{"@value":"Teresa W. Chan"}]},{"@id":"https://cir.nii.ac.jp/crid/1380284922742728068","@type":"Researcher","foaf:name":[{"@value":"Patricia K. Sonsalla"}]},{"@id":"https://cir.nii.ac.jp/crid/1380284922742728067","@type":"Researcher","foaf:name":[{"@value":"Dwight C. German"}]},{"@id":"https://cir.nii.ac.jp/crid/1420282801181441792","@type":"Researcher","personIdentifier":[{"@type":"KAKEN_RESEARCHERS","@value":"00242206"},{"@type":"NRID","@value":"1000000242206"},{"@type":"NRID","@value":"9000003765989"},{"@type":"NRID","@value":"9000411808081"},{"@type":"NRID","@value":"9000008006440"},{"@type":"NRID","@value":"9000413854759"},{"@type":"NRID","@value":"9000412376061"},{"@type":"NRID","@value":"9000000332673"},{"@type":"NRID","@value":"9000409867635"},{"@type":"NRID","@value":"9000253184026"},{"@type":"NRID","@value":"9000309170219"},{"@type":"NRID","@value":"9000411980438"},{"@type":"NRID","@value":"9000252813379"},{"@type":"NRID","@value":"9000241868895"},{"@type":"NRID","@value":"9000020242310"},{"@type":"NRID","@value":"9000399261612"},{"@type":"NRID","@value":"9000411774311"},{"@type":"NRID","@value":"9000369347734"},{"@type":"NRID","@value":"9000018761284"},{"@type":"NRID","@value":"9000413854774"},{"@type":"NRID","@value":"9000253181391"},{"@type":"NRID","@value":"9000010925664"},{"@type":"NRID","@value":"9000367417968"},{"@type":"NRID","@value":"9000255679475"},{"@type":"NRID","@value":"9000413854769"},{"@type":"NRID","@value":"9000252815552"},{"@type":"NRID","@value":"9000018368184"},{"@type":"NRID","@value":"9000321629874"},{"@type":"NRID","@value":"9000411812807"},{"@type":"NRID","@value":"9000405644490"},{"@type":"RESEARCHMAP","@value":"https://researchmap.jp/read0053993"}],"foaf:name":[{"@value":"Hidenori Ichijo"}]},{"@id":"https://cir.nii.ac.jp/crid/1380284922742728075","@type":"Researcher","foaf:name":[{"@value":"Eunsung Junn"}]},{"@id":"https://cir.nii.ac.jp/crid/1380284922742728073","@type":"Researcher","foaf:name":[{"@value":"M. Maral Mouradian"}]}],"contributor":[{"@id":"https://cir.nii.ac.jp/crid/1380284922742728065","@type":"Researcher","foaf:name":[{"@value":"Mark R. Cookson"}],"role":"editor"}],"publication":{"publicationIdentifier":[{"@type":"EISSN","@value":"19326203"}],"prism:publicationName":[{"@value":"PLoS ONE"}],"dc:publisher":[{"@value":"Public Library of Science (PLoS)"}],"prism:publicationDate":"2012-01-10","prism:volume":"7","prism:number":"1","prism:startingPage":"e29935"},"reviewed":"false","dcterms:accessRights":"http://purl.org/coar/access_right/c_abf2","dc:rights":["http://creativecommons.org/licenses/by/4.0/"],"url":[{"@id":"http://dx.plos.org/10.1371/journal.pone.0029935"}],"createdAt":"2012-01-10","modifiedAt":"2025-03-18","foaf:topic":[{"@id":"https://cir.nii.ac.jp/all?q=Science","dc:title":"Science"},{"@id":"https://cir.nii.ac.jp/all?q=MAP%20Kinase%20Kinase%20Kinase%205","dc:title":"MAP Kinase Kinase Kinase 5"},{"@id":"https://cir.nii.ac.jp/all?q=Rats,%20Sprague-Dawley","dc:title":"Rats, 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