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Apoptosis signal-regulating kinase 1 mediates striatal degeneration via the regulation of C1q
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 lesion...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4700432/ https://www.ncbi.nlm.nih.gov/pubmed/26728245 http://dx.doi.org/10.1038/srep18840 |
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author | Cho, Kyoung Joo Cheon, So Young Kim, Gyung Whan |
author_facet | Cho, Kyoung Joo Cheon, So Young Kim, Gyung Whan |
author_sort | Cho, Kyoung Joo |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-4700432 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-47004322016-01-13 Apoptosis signal-regulating kinase 1 mediates striatal degeneration via the regulation of C1q Cho, Kyoung Joo Cheon, So Young Kim, Gyung Whan Sci Rep Article 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. Nature Publishing Group 2016-01-05 /pmc/articles/PMC4700432/ /pubmed/26728245 http://dx.doi.org/10.1038/srep18840 Text en Copyright © 2016, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Cho, Kyoung Joo Cheon, So Young Kim, Gyung Whan Apoptosis signal-regulating kinase 1 mediates striatal degeneration via the regulation of C1q |
title | Apoptosis signal-regulating kinase 1 mediates striatal degeneration via the regulation of C1q |
title_full | Apoptosis signal-regulating kinase 1 mediates striatal degeneration via the regulation of C1q |
title_fullStr | Apoptosis signal-regulating kinase 1 mediates striatal degeneration via the regulation of C1q |
title_full_unstemmed | Apoptosis signal-regulating kinase 1 mediates striatal degeneration via the regulation of C1q |
title_short | Apoptosis signal-regulating kinase 1 mediates striatal degeneration via the regulation of C1q |
title_sort | apoptosis signal-regulating kinase 1 mediates striatal degeneration via the regulation of c1q |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4700432/ https://www.ncbi.nlm.nih.gov/pubmed/26728245 http://dx.doi.org/10.1038/srep18840 |
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