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Axon Injury-Induced Autophagy Activation Is Impaired in a C. elegans Model of Tauopathy
Autophagy is a conserved pathway that plays a key role in cell homeostasis in normal settings, as well as abnormal and stress conditions. Autophagy dysfunction is found in various neurodegenerative diseases, although it remains unclear whether autophagy impairment is a contributor or consequence of...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7696692/ https://www.ncbi.nlm.nih.gov/pubmed/33202845 http://dx.doi.org/10.3390/ijms21228559 |
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author | Ko, Su-Hyuk Gonzalez, Gilberto Liu, Zhijie Chen, Lizhen |
author_facet | Ko, Su-Hyuk Gonzalez, Gilberto Liu, Zhijie Chen, Lizhen |
author_sort | Ko, Su-Hyuk |
collection | PubMed |
description | Autophagy is a conserved pathway that plays a key role in cell homeostasis in normal settings, as well as abnormal and stress conditions. Autophagy dysfunction is found in various neurodegenerative diseases, although it remains unclear whether autophagy impairment is a contributor or consequence of neurodegeneration. Axonal injury is an acute neuronal stress that triggers autophagic responses in an age-dependent manner. In this study, we investigate the injury-triggered autophagy response in a C. elegans model of tauopathy. We found that transgenic expression of pro-aggregant Tau, but not the anti-aggregant Tau, abolished axon injury-induced autophagy activation, resulting in a reduced axon regeneration capacity. Furthermore, axonal trafficking of autophagic vesicles were significantly reduced in the animals expressing pro-aggregant F3ΔK280 Tau, indicating that Tau aggregation impairs autophagy regulation. Importantly, the reduced number of total or trafficking autophagic vesicles in the tauopathy model was not restored by the autophagy activator rapamycin. Loss of PTL-1, the sole Tau homologue in C. elegans, also led to impaired injury-induced autophagy activation, but with an increased basal level of autophagic vesicles. Therefore, we have demonstrated that Tau aggregation as well as Tau depletion both lead to disruption of injury-induced autophagy responses, suggesting that aberrant protein aggregation or microtubule dysfunction can modulate autophagy regulation in neurons after injury. |
format | Online Article Text |
id | pubmed-7696692 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-76966922020-11-29 Axon Injury-Induced Autophagy Activation Is Impaired in a C. elegans Model of Tauopathy Ko, Su-Hyuk Gonzalez, Gilberto Liu, Zhijie Chen, Lizhen Int J Mol Sci Article Autophagy is a conserved pathway that plays a key role in cell homeostasis in normal settings, as well as abnormal and stress conditions. Autophagy dysfunction is found in various neurodegenerative diseases, although it remains unclear whether autophagy impairment is a contributor or consequence of neurodegeneration. Axonal injury is an acute neuronal stress that triggers autophagic responses in an age-dependent manner. In this study, we investigate the injury-triggered autophagy response in a C. elegans model of tauopathy. We found that transgenic expression of pro-aggregant Tau, but not the anti-aggregant Tau, abolished axon injury-induced autophagy activation, resulting in a reduced axon regeneration capacity. Furthermore, axonal trafficking of autophagic vesicles were significantly reduced in the animals expressing pro-aggregant F3ΔK280 Tau, indicating that Tau aggregation impairs autophagy regulation. Importantly, the reduced number of total or trafficking autophagic vesicles in the tauopathy model was not restored by the autophagy activator rapamycin. Loss of PTL-1, the sole Tau homologue in C. elegans, also led to impaired injury-induced autophagy activation, but with an increased basal level of autophagic vesicles. Therefore, we have demonstrated that Tau aggregation as well as Tau depletion both lead to disruption of injury-induced autophagy responses, suggesting that aberrant protein aggregation or microtubule dysfunction can modulate autophagy regulation in neurons after injury. MDPI 2020-11-13 /pmc/articles/PMC7696692/ /pubmed/33202845 http://dx.doi.org/10.3390/ijms21228559 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Ko, Su-Hyuk Gonzalez, Gilberto Liu, Zhijie Chen, Lizhen Axon Injury-Induced Autophagy Activation Is Impaired in a C. elegans Model of Tauopathy |
title | Axon Injury-Induced Autophagy Activation Is Impaired in a C. elegans Model of Tauopathy |
title_full | Axon Injury-Induced Autophagy Activation Is Impaired in a C. elegans Model of Tauopathy |
title_fullStr | Axon Injury-Induced Autophagy Activation Is Impaired in a C. elegans Model of Tauopathy |
title_full_unstemmed | Axon Injury-Induced Autophagy Activation Is Impaired in a C. elegans Model of Tauopathy |
title_short | Axon Injury-Induced Autophagy Activation Is Impaired in a C. elegans Model of Tauopathy |
title_sort | axon injury-induced autophagy activation is impaired in a c. elegans model of tauopathy |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7696692/ https://www.ncbi.nlm.nih.gov/pubmed/33202845 http://dx.doi.org/10.3390/ijms21228559 |
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