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Cystatin C as a potential therapeutic mediator against Parkinson's disease via VEGF-induced angiogenesis and enhanced neuronal autophagy in neurovascular units
Zou, Jing; Chen, Zhaoyu; Wei, Xiaobo; Chen, Zhigang; Fu, Yongmei; Yang, Xiaoyan; Chen, Dan; Wang, Rui; Jenner, Peter; Lu, Jia-Hong; Li, Min; Zhang, Zhuohua; Tang, Beisha; Jin, Kunlin; Wang, Qing
2017-06
Source PublicationCELL DEATH & DISEASE
ISSN2041-4889
Volume8
AbstractCystatin C (CYS C, Cst3) is an endogenous cysteine protease inhibitor that plays neuroprotective roles in neurodegenerative diseases. We aimed to explore the association of CYS C with Parkinson's disease (PD) models and investigate its involvement in the role of neurovascular units (NVUs) in PD neuro-pathogenesis. We used A53T alpha-synuclein (SNCA) transgenic mice and 6-hydroxydopamine-lesioned DAergic PC12 cells as experimental PD models to investigate the mechanisms behind this association. The injections of CYS C were administered to the right substantia nigra (SN) of A53T SNCA transgenic mice to measure the effects of CYS C in transgenic A53T SNCA mice. To explore the angiogenesis in vivo and in vitro, we used the chick embryo chorioallantoic membrane (CAM) assay and tube formation (TF) assay. We found that CYS C has a neuroprotective effect in this in vivo PD model. We observed increased VEGF, NURR1 and autophagy markers LC3B and decreased SNCA and apoptosis marker cleaved CASP3 in different brain regions of CYS C-treated A53T SNCA transgenic mice. In vitro, we observed that CYS C-induced VEGF, a secreted protein, attenuated 6-OHDA-lesioned DAergic PC12 cell degeneration by regulating p-PKC-alpha/p-ERK1/2-Nurr1 signaling and inducing autophagy. VEGF-mediated angiogenesis was markedly enhanced in the conditioned media of 6-OHDA-lesioned PC12 cells with CYS C-overexpression, whereas blockage of autophagy in CYS C-overexpressing PC12 cells significantly downregulated VEGF expression and the associated angiogenesis. Our data indicate that CYS C displays dual neuronal-vascular functions, promoting PC12 cell survival and angiogenesis via regulating the level of secreted VEGF in NVUs. Our study provides evidence that may aid in the development of an alternative approach for the treatment of PD through modulation of CYS C-mediated neuronal-vascular pathways.
DOI10.1038/cddis.2017.240
URLView the original
Indexed BySCI
Language英语
WOS Research AreaCell Biology
WOS SubjectCell Biology
WOS IDWOS:000405895200026
PublisherNATURE PUBLISHING GROUP
The Source to ArticleWOS
Fulltext Access
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Cited Times [WOS]:42   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
Recommended Citation
GB/T 7714
Zou, Jing,Chen, Zhaoyu,Wei, Xiaobo,et al. Cystatin C as a potential therapeutic mediator against Parkinson's disease via VEGF-induced angiogenesis and enhanced neuronal autophagy in neurovascular units[J]. CELL DEATH & DISEASE,2017,8.
APA Zou, Jing.,Chen, Zhaoyu.,Wei, Xiaobo.,Chen, Zhigang.,Fu, Yongmei.,...&Wang, Qing.(2017).Cystatin C as a potential therapeutic mediator against Parkinson's disease via VEGF-induced angiogenesis and enhanced neuronal autophagy in neurovascular units.CELL DEATH & DISEASE,8.
MLA Zou, Jing,et al."Cystatin C as a potential therapeutic mediator against Parkinson's disease via VEGF-induced angiogenesis and enhanced neuronal autophagy in neurovascular units".CELL DEATH & DISEASE 8(2017).
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