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      The Regulation of microRNAs in Alzheimer's Disease

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      , , *
      Frontiers in Neurology
      Frontiers Media S.A.
      Alzheimer's disease, , microRNA, biomarker, autophagy

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          Abstract

          MicroRNAs are small non-coding nucleic acids that are responsible for regulating the gene expression by binding to the coding region and 3' and 5' un-translated region of target messenger RNA. Approximately 70% of known microRNAs are expressed in the brain and increasing evidences demonstrate the possible involvement of microRNAs in Alzheimer's disease (AD) according to the statistics. The characteristic symptoms of AD are the progressive loss of memory and cognitive functions due to the deposition of amyloid β (Aβ) peptide, intracellular aggregation of hyperphosphorylated Tau protein, the loss of synapses, and neuroinflammation, as well as dysfunctional autophagy. Therefore, microRNA-mediated regulation for above-mentioned changes may be the potential therapeutic strategies for AD. In this review, the role of specific microRNAs involved in AD and corresponding applications are systematically discussed, including positive effects associated with the reduction of Aβ or Tau protein, the protection of synapses, the inhibition of neuroinflammation, the mitigation of aging, and the induction of autophagy in AD. It will be beneficial to develop effective targets for establishing a cross link between pharmacological intervention and AD in the near future.

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          Most cited references76

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          Micromanagers of gene expression: the potentially widespread influence of metazoan microRNAs.

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            MicroRNAs in neuronal function and dysfunction.

            MicroRNAs (miRNAs) are small noncoding RNA transcripts expressed throughout the brain that can regulate neuronal gene expression at the post-transcriptional level. Here, we provide an overview of the role for miRNAs in brain development and function, and review evidence suggesting that dysfunction in miRNA signaling contributes to neurodevelopment disorders such as Rett and fragile X syndromes, as well as complex behavioral disorders including schizophrenia, depression and drug addiction. A better understanding of how miRNAs influence the development of neuropsychiatric disorders may reveal fundamental insights into the causes of these devastating illnesses and offer novel targets for therapeutic development. Copyright © 2012 Elsevier Ltd. All rights reserved.
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              Inducing Autophagy by Rapamycin Before, but Not After, the Formation of Plaques and Tangles Ameliorates Cognitive Deficits

              Previous studies have shown that inducing autophagy ameliorates early cognitive deficits associated with the build-up of soluble amyloid-β (Aβ). However, the effects of inducing autophagy on plaques and tangles are yet to be determined. While soluble Aβ and tau represent toxic species in Alzheimer's disease (AD) pathogenesis, there is well documented evidence that plaques and tangles also are detrimental to normal brain function. Thus, it is critical to assess the effects of inducing autophagy in an animal model with established plaques and tangles. Here we show that rapamycin, when given prophylactically to 2-month-old 3xTg-AD mice throughout their life, induces autophagy and significantly reduces plaques, tangles and cognitive deficits. In contrast, inducing autophagy in 15-month-old 3xTg-AD mice, which have established plaques and tangles, has no effects on AD-like pathology and cognitive deficits. In conclusion, we show that autophagy induction via rapamycin may represent a valid therapeutic strategy in AD when administered early in the disease progression.
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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
                17 April 2020
                2020
                : 11
                : 288
                Affiliations
                Hubei Key Laboratory of Exercise Training and Monitoring, Tianjiu Research and Development Center for Exercise Nutrition and Foods, College of Health Science, Wuhan Sports University , Wuhan, China
                Author notes

                Edited by: Y-H. Taguchi, Chuo University, Japan

                Reviewed by: Manabu Funayama, Juntendo University, Japan; Liena Elbaghir Omer Elsayed, University of Khartoum, Sudan

                *Correspondence: Ning Chen nchen510@ 123456gmail.com

                This article was submitted to Neurogenetics, a section of the journal Frontiers in Neurology

                Article
                10.3389/fneur.2020.00288
                7180504
                32362867
                8f750237-b120-4e2f-9ac7-5e9c04c8e3be
                Copyright © 2020 Kou, Chen and Chen.

                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
                : 07 January 2020
                : 26 March 2020
                Page count
                Figures: 1, Tables: 0, Equations: 0, References: 113, Pages: 10, Words: 8240
                Funding
                Funded by: National Natural Science Foundation of China 10.13039/501100001809
                Funded by: Natural Science Foundation of Hubei Province 10.13039/501100003819
                Funded by: Hubei Provincial Department of Education 10.13039/100012554
                Categories
                Neurology
                Review

                Neurology
                alzheimer's disease,,microrna,biomarker,autophagy
                Neurology
                alzheimer's disease, , microrna, biomarker, autophagy

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