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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...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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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. |
format | Online Article Text |
id | pubmed-9126031 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
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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