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Apoptosis signal-regulating kinase 1 mediates striatal degeneration via the regulation of C1q

Authors
 Kyoung Joo Cho  ;  So Young Cheon  ;  Gyung Whan Kim 
Citation
 SCIENTIFIC REPORTS, Vol.6 : 18840, 2016 
Journal Title
SCIENTIFIC REPORTS
Issue Date
2016
MeSH
Animals ; Astrocytes/metabolism ; Cell Death ; Complement C1q/immunology* ; Corpus Striatum/immunology* ; Corpus Striatum/metabolism* ; Corpus Striatum/pathology ; Dendrites/metabolism ; Dendrites/pathology ; Disease Models, Animal ; Down-Regulation ; Gene Expression Regulation ; MAP Kinase Kinase Kinase 5/genetics ; MAP Kinase Kinase Kinase 5/metabolism* ; Male ; Membrane Glycoproteins/genetics ; Membrane Glycoproteins/metabolism ; Mice ; Neurodegenerative Diseases/genetics ; Neurodegenerative Diseases/immunology ; Neurodegenerative Diseases/metabolism ; Neurodegenerative Diseases/pathology ; Neurons/metabolism ; Nitro Compounds/adverse effects ; Propionates/adverse effects ; Receptors, Complement/genetics ; Receptors, Complement/metabolism ; Transforming Growth Factor beta1/metabolism
Abstract
Apoptosis signal-regulating kinase-1 (ASK1), an early signaling element in the cell death pathway, has been hypothesized to participate in the pathology of neurodegenerative diseases. The systemic administration of 3-nitropropionic acid (3-NP) facilitates the development of selective striatal lesions. However, it remains unclear whether specific neurons are selectively targeted in 3-NP-infused striatal degeneration. Recently, it has been proposed that complement-mediated synapse elimination may be reactivated aberrantly in the pathology of neurodegenerative diseases. We hypothesized that ASK1 is involved in striatal astrocyte reactivation; reactive astrocyte secretes molecules detrimental to neuron; and striatal neurons are more susceptible to these factors. Our results indicate that striatal astrocyte is reactivated and ASK1 level increases after 3-NP general and chronic infusion. Reactive striatal astrocyte increases TGF-beta differentially to cortex and striatum. ASK1 may be involved in regulation of astrocyte TGF-beta and it is linked to the C1q level in spatial and temporal, and moreover in the earlier stage of progressing striatal neuronal loss. Conclusively the present study suggests that ASK1 mediates 3-NP toxicity and regulates C1q level through the astrocyte TGF-beta. And also it may suggest that C1q level may be a surrogate of prediction marker representing neurodegenerative disease progress before developing behavioral impairment.
Files in This Item:
T201601453.pdf Download
DOI
10.1038/srep18840
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Neurology (신경과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Gyung Whan(김경환) ORCID logo https://orcid.org/0000-0001-7053-4372
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/146844
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