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      Non-coding RNAs: The Neuroinflammatory Regulators in Neurodegenerative Diseases

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          Abstract

          As a common indication of nervous system diseases, neuroinflammation has attracted more and more attention, especially in the process of a variety of neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease. Two types of non-coding RNAs (ncRNAs) are widely involved in the process of neuroinflammation in neurodegenerative diseases, namely long non-coding RNAs (lncRNAs) and microRNAs (miRNAs). However, no research has systematically summarized that lncRNAs and miRNAs regulate neurodegenerative diseases through neuroinflammatory mechanisms. In this study, we summarize four main mechanisms of lncRNAs and miRNAs involved in neuroinflammation in neurodegenerative diseases, including the imbalance between proinflammatory and neuroprotective cells in microglia and astrocytes, NLRP3 inflammasome, oxidative stress, and mitochondrial dysfunction, and inflammatory mediators. We hope to clarify the regulatory mechanism of lncRNAs and miRNAs in neurodegenerative diseases and provide new insights into the etiological treatment of neurodegenerative diseases from the perspective of neuroinflammation.

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          Most cited references129

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          MicroRNAs: target recognition and regulatory functions.

          MicroRNAs (miRNAs) are endogenous approximately 23 nt RNAs that play important gene-regulatory roles in animals and plants by pairing to the mRNAs of protein-coding genes to direct their posttranscriptional repression. This review outlines the current understanding of miRNA target recognition in animals and discusses the widespread impact of miRNAs on both the expression and evolution of protein-coding genes.
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            A role for mitochondria in NLRP3 inflammasome activation.

            An inflammatory response initiated by the NLRP3 inflammasome is triggered by a variety of situations of host 'danger', including infection and metabolic dysregulation. Previous studies suggested that NLRP3 inflammasome activity is negatively regulated by autophagy and positively regulated by reactive oxygen species (ROS) derived from an uncharacterized organelle. Here we show that mitophagy/autophagy blockade leads to the accumulation of damaged, ROS-generating mitochondria, and this in turn activates the NLRP3 inflammasome. Resting NLRP3 localizes to endoplasmic reticulum structures, whereas on inflammasome activation both NLRP3 and its adaptor ASC redistribute to the perinuclear space where they co-localize with endoplasmic reticulum and mitochondria organelle clusters. Notably, both ROS generation and inflammasome activation are suppressed when mitochondrial activity is dysregulated by inhibition of the voltage-dependent anion channel. This indicates that NLRP3 inflammasome senses mitochondrial dysfunction and may explain the frequent association of mitochondrial damage with inflammatory diseases.
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              The NLRP3 Inflammasome: An Overview of Mechanisms of Activation and Regulation

              The NLRP3 inflammasome is a critical component of the innate immune system that mediates caspase-1 activation and the secretion of proinflammatory cytokines IL-1β/IL-18 in response to microbial infection and cellular damage. However, the aberrant activation of the NLRP3 inflammasome has been linked with several inflammatory disorders, which include cryopyrin-associated periodic syndromes, Alzheimer’s disease, diabetes, and atherosclerosis. The NLRP3 inflammasome is activated by diverse stimuli, and multiple molecular and cellular events, including ionic flux, mitochondrial dysfunction, and the production of reactive oxygen species, and lysosomal damage have been shown to trigger its activation. How NLRP3 responds to those signaling events and initiates the assembly of the NLRP3 inflammasome is not fully understood. In this review, we summarize our current understanding of the mechanisms of NLRP3 inflammasome activation by multiple signaling events, and its regulation by post-translational modifications and interacting partners of NLRP3.
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                Author and article information

                Contributors
                Journal
                Front Neurol
                Front Neurol
                Front. Neurol.
                Frontiers in Neurology
                Frontiers Media S.A.
                1664-2295
                12 August 2022
                2022
                : 13
                : 929290
                Affiliations
                [1] 1Department of Neurology, Xiangya Hospital, Central South University , Changsha, China
                [2] 2Xiangya School of Medicine, Central South University , Changsha, China
                [3] 3National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University , Changsha, China
                [4] 4Clinical Research Center for Epileptic Disease of Hunan Province, Central South University , Changsha, China
                [5] 5Department of Geriatrics, The Second Xiangya Hospital of Central South University , Changsha, China
                Author notes

                Edited by: Shaowu Cheng, Hunan University of Chinese Medicine, China

                Reviewed by: Wenyu Liu, Sichuan University, China; Yam Nath Paudel, Independent Researcher, Sydney, NSW, Australia; Shengde Li, Peking Union Medical College Hospital (CAMS), China

                *Correspondence: Wenbiao Xiao xiaowb7821@ 123456csu.edu.cn

                This article was submitted to Multiple Sclerosis and Neuroimmunology, a section of the journal Frontiers in Neurology

                Article
                10.3389/fneur.2022.929290
                9414873
                36034298
                b80d848d-0c23-46f3-b8bf-68f097d1a5f7
                Copyright © 2022 Jiang, Zhang, Yue, Shi, Xiao, Xiao and Luo.

                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.

                History
                : 26 April 2022
                : 23 June 2022
                Page count
                Figures: 4, Tables: 0, Equations: 0, References: 130, Pages: 15, Words: 10598
                Funding
                Funded by: National Natural Science Foundation of China, doi 10.13039/501100001809;
                Award ID: 81974206
                Categories
                Neurology
                Review

                Neurology
                ncrna,neuroinflammation,neurodegenerative diseases,microglia,nlrp3,oxidative stress
                Neurology
                ncrna, neuroinflammation, neurodegenerative diseases, microglia, nlrp3, oxidative stress

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