Abnormal mitochondria in a non-human primate model of MPTP-induced Parkinson's disease: Drp1 and CDK5/p25 signaling = 원숭이 파킨슨병 모델 뇌조직내 미토콘드리아 손상이 Drp1과 CDK5/p25 신호전달과 관련

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Title
Abnormal mitochondria in a non-human primate model of MPTP-induced Parkinson's disease: Drp1 and CDK5/p25 signaling = 원숭이 파킨슨병 모델 뇌조직내 미토콘드리아 손상이 Drp1과 CDK5/p25 신호전달과 관련
Author(s)
Junghyung Park; Jincheol Seo; Jinyoung Won; Hyeon-Gu Yeo; Yu-Jin Ahn; Keonwoo Kim; Yeung Bae Jin; Bon Sang KooKyung Seob LimKang Jin JeongPhilyong KangHwal Yong LeeSeung Ho BaekChang Yeop JeonJung Joo HongJae Won HuhYoung-Hyun KimSang Je ParkSun-Uk Kim; D S Lee; Sang-Rae Lee; Youngjeon Lee
Bibliographic Citation
Experimental Neurobiology, vol. 28, no. 3, pp. 414-424
Publication Year
2019
Abstract
Mitochondria continuously fuse and divide to maintain homeostasis. An impairment in the balance between the fusion and fission processes can trigger mitochondrial dysfunction. Accumulating evidence suggests that mitochondrial dysfunction is related to neurodegenerative diseases such as Parkinson's disease (PD), with excessive mitochondrial fission in dopaminergic neurons being one of the pathological mechanisms of PD. Here, we investigated the balance between mitochondrial fusion and fission in the substantia nigra of a non-human primate model of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD. We found that MPTP induced shorter and abnormally distributed mitochondria. This phenomenon was accompanied by the activation of dynamin-related protein 1 (Drp1), a mitochondrial fission protein, through increased phosphorylation at S616. Thereafter, we assessed for activation of the components of the cyclin-dependent kinase 5 (CDK5) and extracellular signal-regulated kinase (ERK) signaling cascades, which are known regulators of Drp1(S616) phosphorylation. MPTP induced an increase in p25 and p35, which are required for CDK5 activation. Together, these findings suggest that the phosphorylation of Drp1(S616) by CDK5 is involved in mitochondrial fission in the substantia nigra of a non-human primate model of MPTP-induced PD.
Keyword
Cyclin-dependent kinasesMitochondriaMitochondrial dynamicsNon-human primateParkinson disease
ISSN
1226-2560
Publisher
South Korea
DOI
http://dx.doi.org/10.5607/en.2019.28.3.414
Type
Article
Appears in Collections:
Ochang Branch Institute > Division of Bioinfrastructure > National Primate Research Center > 1. Journal Articles
Ochang Branch Institute > Division of Bioinfrastructure > Futuristic Animal Resource & Research Center > 1. Journal Articles
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