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Potential Mechanism Underlying Exercise Upregulated Circulating Blood Exosome miR-215-5p to Prevent Necroptosis of Neuronal Cells and a Model for Early Diagnosis of Alzheimer’s Disease

Exercise is crucial for preventing Alzheimer’s disease (AD), although the exact underlying mechanism remains unclear. The construction of an accurate AD risk prediction model is beneficial as it can provide a theoretical basis for preventive exercise prescription. In recent years, necroptosis has be...

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Autores principales: Chen, Yisheng, Sun, Yaying, Luo, Zhiwen, Lin, Jinrong, Qi, Beijie, Kang, Xueran, Ying, Chenting, Guo, Chenyang, Yao, Mengxuan, Chen, Xiangjun, Wang, Yi, Wang, Qian, Chen, Jiwu, Chen, Shiyi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9126031/
https://www.ncbi.nlm.nih.gov/pubmed/35615585
http://dx.doi.org/10.3389/fnagi.2022.860364
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author Chen, Yisheng
Sun, Yaying
Luo, Zhiwen
Lin, Jinrong
Qi, Beijie
Kang, Xueran
Ying, Chenting
Guo, Chenyang
Yao, Mengxuan
Chen, Xiangjun
Wang, Yi
Wang, Qian
Chen, Jiwu
Chen, Shiyi
author_facet Chen, Yisheng
Sun, Yaying
Luo, Zhiwen
Lin, Jinrong
Qi, Beijie
Kang, Xueran
Ying, Chenting
Guo, Chenyang
Yao, Mengxuan
Chen, Xiangjun
Wang, Yi
Wang, Qian
Chen, Jiwu
Chen, Shiyi
author_sort Chen, Yisheng
collection PubMed
description Exercise is crucial for preventing Alzheimer’s disease (AD), although the exact underlying mechanism remains unclear. The construction of an accurate AD risk prediction model is beneficial as it can provide a theoretical basis for preventive exercise prescription. In recent years, necroptosis has been confirmed as an important manifestation of AD, and exercise is known to inhibit necroptosis of neuronal cells. In this study, we extracted 67 necroptosis-related genes and 32 necroptosis-related lncRNAs and screened for key predictive AD risk genes through a random forest analysis. Based on the neural network Prediction model, we constructed a new logistic regression-based AD risk prediction model in order to provide a visual basis for the formulation of exercise prescription. The prediction model had an area under the curve (AUC) value of 0.979, indicative of strong predictive power and a robust clinical application prospect. In the exercise group, the expression of exosomal miR-215-5p was found to be upregulated; miR-215-5p could potentially inhibit the expressions of IDH1, BCL2L11, and SIRT1. The single-cell SCENIC assay was used to identify key transcriptional regulators in skeletal muscle. Among them, CEBPB and GATA6 were identified as putative transcriptional regulators of miR-215. After “skeletal muscle removal of load,” the expressions of CEBPB and GATA6 increased substantially, which in turn led to the elevation of miR-215 expression, thereby suggesting a putative mechanism for negative feedback regulation of exosomal homeostasis.
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spelling pubmed-91260312022-05-24 Potential Mechanism Underlying Exercise Upregulated Circulating Blood Exosome miR-215-5p to Prevent Necroptosis of Neuronal Cells and a Model for Early Diagnosis of Alzheimer’s Disease Chen, Yisheng Sun, Yaying Luo, Zhiwen Lin, Jinrong Qi, Beijie Kang, Xueran Ying, Chenting Guo, Chenyang Yao, Mengxuan Chen, Xiangjun Wang, Yi Wang, Qian Chen, Jiwu Chen, Shiyi Front Aging Neurosci Neuroscience Exercise is crucial for preventing Alzheimer’s disease (AD), although the exact underlying mechanism remains unclear. The construction of an accurate AD risk prediction model is beneficial as it can provide a theoretical basis for preventive exercise prescription. In recent years, necroptosis has been confirmed as an important manifestation of AD, and exercise is known to inhibit necroptosis of neuronal cells. In this study, we extracted 67 necroptosis-related genes and 32 necroptosis-related lncRNAs and screened for key predictive AD risk genes through a random forest analysis. Based on the neural network Prediction model, we constructed a new logistic regression-based AD risk prediction model in order to provide a visual basis for the formulation of exercise prescription. The prediction model had an area under the curve (AUC) value of 0.979, indicative of strong predictive power and a robust clinical application prospect. In the exercise group, the expression of exosomal miR-215-5p was found to be upregulated; miR-215-5p could potentially inhibit the expressions of IDH1, BCL2L11, and SIRT1. The single-cell SCENIC assay was used to identify key transcriptional regulators in skeletal muscle. Among them, CEBPB and GATA6 were identified as putative transcriptional regulators of miR-215. After “skeletal muscle removal of load,” the expressions of CEBPB and GATA6 increased substantially, which in turn led to the elevation of miR-215 expression, thereby suggesting a putative mechanism for negative feedback regulation of exosomal homeostasis. Frontiers Media S.A. 2022-05-09 /pmc/articles/PMC9126031/ /pubmed/35615585 http://dx.doi.org/10.3389/fnagi.2022.860364 Text en Copyright © 2022 Chen, Sun, Luo, Lin, Qi, Kang, Ying, Guo, Yao, Chen, Wang, Wang, Chen and Chen. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Chen, Yisheng
Sun, Yaying
Luo, Zhiwen
Lin, Jinrong
Qi, Beijie
Kang, Xueran
Ying, Chenting
Guo, Chenyang
Yao, Mengxuan
Chen, Xiangjun
Wang, Yi
Wang, Qian
Chen, Jiwu
Chen, Shiyi
Potential Mechanism Underlying Exercise Upregulated Circulating Blood Exosome miR-215-5p to Prevent Necroptosis of Neuronal Cells and a Model for Early Diagnosis of Alzheimer’s Disease
title Potential Mechanism Underlying Exercise Upregulated Circulating Blood Exosome miR-215-5p to Prevent Necroptosis of Neuronal Cells and a Model for Early Diagnosis of Alzheimer’s Disease
title_full Potential Mechanism Underlying Exercise Upregulated Circulating Blood Exosome miR-215-5p to Prevent Necroptosis of Neuronal Cells and a Model for Early Diagnosis of Alzheimer’s Disease
title_fullStr Potential Mechanism Underlying Exercise Upregulated Circulating Blood Exosome miR-215-5p to Prevent Necroptosis of Neuronal Cells and a Model for Early Diagnosis of Alzheimer’s Disease
title_full_unstemmed Potential Mechanism Underlying Exercise Upregulated Circulating Blood Exosome miR-215-5p to Prevent Necroptosis of Neuronal Cells and a Model for Early Diagnosis of Alzheimer’s Disease
title_short Potential Mechanism Underlying Exercise Upregulated Circulating Blood Exosome miR-215-5p to Prevent Necroptosis of Neuronal Cells and a Model for Early Diagnosis of Alzheimer’s Disease
title_sort potential mechanism underlying exercise upregulated circulating blood exosome mir-215-5p to prevent necroptosis of neuronal cells and a model for early diagnosis of alzheimer’s disease
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9126031/
https://www.ncbi.nlm.nih.gov/pubmed/35615585
http://dx.doi.org/10.3389/fnagi.2022.860364
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