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miR-204 silencing reduces mitochondrial autophagy and ROS production in a murine AD model via the TRPML1-activated STAT3 pathway

Mitochondrial dysfunction is an early feature of Alzheimer’s disease (AD), whereby accumulation of damaged mitochondria in conjunction with impaired mitophagy contributes to neurodegeneration. Various non-transcribed microRNAs (miRNAs) are involved in this process. In the present study, we aimed to...

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Autores principales: Zhang, Lu, Fang, Yu, Zhao, Xinyu, Zheng, Yake, Ma, Yunqing, Li, Shuang, Huang, Zhi, Li, Lihao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society of Gene & Cell Therapy 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8121631/
https://www.ncbi.nlm.nih.gov/pubmed/34026326
http://dx.doi.org/10.1016/j.omtn.2021.02.010
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author Zhang, Lu
Fang, Yu
Zhao, Xinyu
Zheng, Yake
Ma, Yunqing
Li, Shuang
Huang, Zhi
Li, Lihao
author_facet Zhang, Lu
Fang, Yu
Zhao, Xinyu
Zheng, Yake
Ma, Yunqing
Li, Shuang
Huang, Zhi
Li, Lihao
author_sort Zhang, Lu
collection PubMed
description Mitochondrial dysfunction is an early feature of Alzheimer’s disease (AD), whereby accumulation of damaged mitochondria in conjunction with impaired mitophagy contributes to neurodegeneration. Various non-transcribed microRNAs (miRNAs) are involved in this process. In the present study, we aimed to decipher the participation of miR-204 in a murine AD model. Primary hippocampal neurons were isolated from mice and treated with β-amyloid 1-42 (Aβ1-42) to establish a cell model of AD. Dichloro-dihydro-fluorescein diacetate and dihydrorhodamine 123 staining assays were performed to measure total reactive oxygen species (ROS) and mitochondrial ROS production in neurons, and MitoSOX staining was done to analyze mitochondrial ROS production in hippocampus. Furthermore, mitochondrial autophagy was observed in hippocampus from amyloid precursor protein/pesenilin-1 AD modeled mice, and their cognitive function was assessed by Morris water maze. Mitochondrial damage, ROS production, and mitochondrial autophagy were observed in AD cell model induced by Aβ1-42. In AD, signal transducer and activator of transcription 3 (STAT3) and transient receptor potential mucolipin-1 (TRPML1) expression was downregulated, although miR-204 expression was upregulated. TRPML1 overexpression, downregulation of miR-204, or STAT3 pathway activation reduced the Aβ1-42-induced mitochondrial damage, along with ROS production and mitochondrial autophagy in vivo and in vitro. Silencing of miR-204 could upregulate TRPML1 expression, thus suppressing ROS production and mitochondrial autophagy in AD through STAT3 pathway.
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spelling pubmed-81216312021-05-21 miR-204 silencing reduces mitochondrial autophagy and ROS production in a murine AD model via the TRPML1-activated STAT3 pathway Zhang, Lu Fang, Yu Zhao, Xinyu Zheng, Yake Ma, Yunqing Li, Shuang Huang, Zhi Li, Lihao Mol Ther Nucleic Acids Original Article Mitochondrial dysfunction is an early feature of Alzheimer’s disease (AD), whereby accumulation of damaged mitochondria in conjunction with impaired mitophagy contributes to neurodegeneration. Various non-transcribed microRNAs (miRNAs) are involved in this process. In the present study, we aimed to decipher the participation of miR-204 in a murine AD model. Primary hippocampal neurons were isolated from mice and treated with β-amyloid 1-42 (Aβ1-42) to establish a cell model of AD. Dichloro-dihydro-fluorescein diacetate and dihydrorhodamine 123 staining assays were performed to measure total reactive oxygen species (ROS) and mitochondrial ROS production in neurons, and MitoSOX staining was done to analyze mitochondrial ROS production in hippocampus. Furthermore, mitochondrial autophagy was observed in hippocampus from amyloid precursor protein/pesenilin-1 AD modeled mice, and their cognitive function was assessed by Morris water maze. Mitochondrial damage, ROS production, and mitochondrial autophagy were observed in AD cell model induced by Aβ1-42. In AD, signal transducer and activator of transcription 3 (STAT3) and transient receptor potential mucolipin-1 (TRPML1) expression was downregulated, although miR-204 expression was upregulated. TRPML1 overexpression, downregulation of miR-204, or STAT3 pathway activation reduced the Aβ1-42-induced mitochondrial damage, along with ROS production and mitochondrial autophagy in vivo and in vitro. Silencing of miR-204 could upregulate TRPML1 expression, thus suppressing ROS production and mitochondrial autophagy in AD through STAT3 pathway. American Society of Gene & Cell Therapy 2021-02-15 /pmc/articles/PMC8121631/ /pubmed/34026326 http://dx.doi.org/10.1016/j.omtn.2021.02.010 Text en © 2021 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Original Article
Zhang, Lu
Fang, Yu
Zhao, Xinyu
Zheng, Yake
Ma, Yunqing
Li, Shuang
Huang, Zhi
Li, Lihao
miR-204 silencing reduces mitochondrial autophagy and ROS production in a murine AD model via the TRPML1-activated STAT3 pathway
title miR-204 silencing reduces mitochondrial autophagy and ROS production in a murine AD model via the TRPML1-activated STAT3 pathway
title_full miR-204 silencing reduces mitochondrial autophagy and ROS production in a murine AD model via the TRPML1-activated STAT3 pathway
title_fullStr miR-204 silencing reduces mitochondrial autophagy and ROS production in a murine AD model via the TRPML1-activated STAT3 pathway
title_full_unstemmed miR-204 silencing reduces mitochondrial autophagy and ROS production in a murine AD model via the TRPML1-activated STAT3 pathway
title_short miR-204 silencing reduces mitochondrial autophagy and ROS production in a murine AD model via the TRPML1-activated STAT3 pathway
title_sort mir-204 silencing reduces mitochondrial autophagy and ros production in a murine ad model via the trpml1-activated stat3 pathway
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8121631/
https://www.ncbi.nlm.nih.gov/pubmed/34026326
http://dx.doi.org/10.1016/j.omtn.2021.02.010
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