miR-204-3p/Nox4 Mediates Memory Deficits in a Mouse Model of Alzheimer’s Disease
Alzheimer’s disease (AD) is the most common neurodegenerative disorder leading to dementia in the elderly, and the mechanisms of AD are not fully defined. MicroRNAs (miRNAs) have been shown to contribute to memory deficits in AD. In this study, we identified that miR-204-3p was downregulated in the...
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| Veröffentlicht in: | Molecular therapy 2021-01, Vol.29 (1), p.396-408 |
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| creator | Tao, Wenyuan Yu, Linjie Shu, Shu Liu, Ying Zhuang, Zi Xu, Siyi Bao, Xinyu Gu, Yue Cai, Fang Song, Weihong Xu, Yun Zhu, Xiaolei |
| description | Alzheimer’s disease (AD) is the most common neurodegenerative disorder leading to dementia in the elderly, and the mechanisms of AD are not fully defined. MicroRNAs (miRNAs) have been shown to contribute to memory deficits in AD. In this study, we identified that miR-204-3p was downregulated in the hippocampus and plasma of 6-month-old APPswe/PS1dE9 (APP/PS1) mice. miR-204-3p overexpression attenuated memory and synaptic deficits in APP/PS1 mice. The amyloid levels and oxidative stress were decreased in the hippocampus of APP/PS1 mice after miR-204-3p overexpression. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 4 (Nox4) was a target of miR-204-3p, and Nox4 inhibition by GLX351322 protected neuronal cells against Aβ1–42-induced neurotoxicity. Furthermore, GLX351322 treatment rescued synaptic and memory deficits, and decreased oxidative stress and amyloid levels in the hippocampus of APP/PS1 mice. These results revealed that miR-204-3p attenuated memory deficits and oxidative stress in APP/PS1 mice by targeting Nox4, and miR-204-3p overexpression and/or Nox4 inhibition might be a potential therapeutic strategy for AD treatment.
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Zhu and colleagues demonstrate that miR-204-3p attenuates memory and synaptic deficits in APPswe/PS1dE9 (APP/PS1) mice via inhibition of NADPH oxidase 4 (Nox4). In addition, Nox4 inhibition by GLX351322 rescues memory deficits in APP/PS1 mice, suggesting that miR-204-3p overexpression and/or Nox4 inhibition is a potential therapeutic strategy for Alzheimer’s disease treatment. |
| doi_str_mv | 10.1016/j.ymthe.2020.09.006 |
| format | Article |
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[Display omitted]
Zhu and colleagues demonstrate that miR-204-3p attenuates memory and synaptic deficits in APPswe/PS1dE9 (APP/PS1) mice via inhibition of NADPH oxidase 4 (Nox4). In addition, Nox4 inhibition by GLX351322 rescues memory deficits in APP/PS1 mice, suggesting that miR-204-3p overexpression and/or Nox4 inhibition is a potential therapeutic strategy for Alzheimer’s disease treatment.</description><identifier>ISSN: 1525-0016</identifier><identifier>EISSN: 1525-0024</identifier><identifier>DOI: 10.1016/j.ymthe.2020.09.006</identifier><identifier>PMID: 32950103</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Alzheimer Disease - complications ; Alzheimer Disease - genetics ; Alzheimer’s disease ; Amyloid beta-Peptides - metabolism ; Animals ; beta amyloid ; Biomarkers ; Disease Models, Animal ; Disease Susceptibility ; memory deficits ; Memory Disorders - diagnosis ; Memory Disorders - etiology ; Mice ; Mice, Transgenic ; MicroRNAs - genetics ; miR-204-3p ; NADPH Oxidase 4 - genetics ; Nox4 ; Original ; Oxidative Stress ; synaptic dysfunction</subject><ispartof>Molecular therapy, 2021-01, Vol.29 (1), p.396-408</ispartof><rights>2020 The American Society of Gene and Cell Therapy</rights><rights>Copyright © 2020 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.</rights><rights>2020 The American Society of Gene and Cell Therapy. 2020 The American Society of Gene and Cell Therapy</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c525t-a8886ec0a2657c0a6222e514169edf94120cd0760da73e37719052147569a5493</citedby><cites>FETCH-LOGICAL-c525t-a8886ec0a2657c0a6222e514169edf94120cd0760da73e37719052147569a5493</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7791017/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7791017/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32950103$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Tao, Wenyuan</creatorcontrib><creatorcontrib>Yu, Linjie</creatorcontrib><creatorcontrib>Shu, Shu</creatorcontrib><creatorcontrib>Liu, Ying</creatorcontrib><creatorcontrib>Zhuang, Zi</creatorcontrib><creatorcontrib>Xu, Siyi</creatorcontrib><creatorcontrib>Bao, Xinyu</creatorcontrib><creatorcontrib>Gu, Yue</creatorcontrib><creatorcontrib>Cai, Fang</creatorcontrib><creatorcontrib>Song, Weihong</creatorcontrib><creatorcontrib>Xu, Yun</creatorcontrib><creatorcontrib>Zhu, Xiaolei</creatorcontrib><title>miR-204-3p/Nox4 Mediates Memory Deficits in a Mouse Model of Alzheimer’s Disease</title><title>Molecular therapy</title><addtitle>Mol Ther</addtitle><description>Alzheimer’s disease (AD) is the most common neurodegenerative disorder leading to dementia in the elderly, and the mechanisms of AD are not fully defined. MicroRNAs (miRNAs) have been shown to contribute to memory deficits in AD. In this study, we identified that miR-204-3p was downregulated in the hippocampus and plasma of 6-month-old APPswe/PS1dE9 (APP/PS1) mice. miR-204-3p overexpression attenuated memory and synaptic deficits in APP/PS1 mice. The amyloid levels and oxidative stress were decreased in the hippocampus of APP/PS1 mice after miR-204-3p overexpression. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 4 (Nox4) was a target of miR-204-3p, and Nox4 inhibition by GLX351322 protected neuronal cells against Aβ1–42-induced neurotoxicity. Furthermore, GLX351322 treatment rescued synaptic and memory deficits, and decreased oxidative stress and amyloid levels in the hippocampus of APP/PS1 mice. These results revealed that miR-204-3p attenuated memory deficits and oxidative stress in APP/PS1 mice by targeting Nox4, and miR-204-3p overexpression and/or Nox4 inhibition might be a potential therapeutic strategy for AD treatment.
[Display omitted]
Zhu and colleagues demonstrate that miR-204-3p attenuates memory and synaptic deficits in APPswe/PS1dE9 (APP/PS1) mice via inhibition of NADPH oxidase 4 (Nox4). In addition, Nox4 inhibition by GLX351322 rescues memory deficits in APP/PS1 mice, suggesting that miR-204-3p overexpression and/or Nox4 inhibition is a potential therapeutic strategy for Alzheimer’s disease treatment.</description><subject>Alzheimer Disease - complications</subject><subject>Alzheimer Disease - genetics</subject><subject>Alzheimer’s disease</subject><subject>Amyloid beta-Peptides - metabolism</subject><subject>Animals</subject><subject>beta amyloid</subject><subject>Biomarkers</subject><subject>Disease Models, Animal</subject><subject>Disease Susceptibility</subject><subject>memory deficits</subject><subject>Memory Disorders - diagnosis</subject><subject>Memory Disorders - etiology</subject><subject>Mice</subject><subject>Mice, Transgenic</subject><subject>MicroRNAs - genetics</subject><subject>miR-204-3p</subject><subject>NADPH Oxidase 4 - genetics</subject><subject>Nox4</subject><subject>Original</subject><subject>Oxidative Stress</subject><subject>synaptic dysfunction</subject><issn>1525-0016</issn><issn>1525-0024</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kN1KAzEQhYMo1r8nEGRfYLeT7CZpLhTE-gdVoeh1iNlZm9LtlmQt1itfw9fzSUytFr3xZuZA5pzJfIQcUsgoUNEdZ4u6HWHGgEEGKgMQG2SHcsZTAFZsrjUVHbIbwjgqypXYJp2cKQ4U8h0yrN0wZVCk-ax727wUyQ2WzrQYoqgbv0j6WDnr2pC4aWKSm-Y5YKwlTpKmSk4nryN0NfqPt_eQ9F1AE3CfbFVmEvDgu--Rh4vz-7OrdHB3eX12Okht_Fabml6vJ9CCYYLL2ARjDDktqFBYVqqgDGwJUkBpZI65lFQBZ7SQXCjDC5XvkZNV7uz5scbS4rT1ZqJn3tXGL3RjnP77MnUj_dTMtZQqApQxIF8FWN-E4LFaeynoJWI91l-I9RKxBqUj4ug6-r127flhGgeOVwMYj5879DpYh1MbwXq0rS4b9--CT4SnjVE</recordid><startdate>20210106</startdate><enddate>20210106</enddate><creator>Tao, Wenyuan</creator><creator>Yu, Linjie</creator><creator>Shu, Shu</creator><creator>Liu, Ying</creator><creator>Zhuang, Zi</creator><creator>Xu, Siyi</creator><creator>Bao, Xinyu</creator><creator>Gu, Yue</creator><creator>Cai, Fang</creator><creator>Song, Weihong</creator><creator>Xu, Yun</creator><creator>Zhu, Xiaolei</creator><general>Elsevier Inc</general><general>American Society of Gene & Cell Therapy</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>5PM</scope></search><sort><creationdate>20210106</creationdate><title>miR-204-3p/Nox4 Mediates Memory Deficits in a Mouse Model of Alzheimer’s Disease</title><author>Tao, Wenyuan ; Yu, Linjie ; Shu, Shu ; Liu, Ying ; Zhuang, Zi ; Xu, Siyi ; Bao, Xinyu ; Gu, Yue ; Cai, Fang ; Song, Weihong ; Xu, Yun ; Zhu, Xiaolei</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c525t-a8886ec0a2657c0a6222e514169edf94120cd0760da73e37719052147569a5493</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Alzheimer Disease - complications</topic><topic>Alzheimer Disease - genetics</topic><topic>Alzheimer’s disease</topic><topic>Amyloid beta-Peptides - metabolism</topic><topic>Animals</topic><topic>beta amyloid</topic><topic>Biomarkers</topic><topic>Disease Models, Animal</topic><topic>Disease Susceptibility</topic><topic>memory deficits</topic><topic>Memory Disorders - diagnosis</topic><topic>Memory Disorders - etiology</topic><topic>Mice</topic><topic>Mice, Transgenic</topic><topic>MicroRNAs - genetics</topic><topic>miR-204-3p</topic><topic>NADPH Oxidase 4 - genetics</topic><topic>Nox4</topic><topic>Original</topic><topic>Oxidative Stress</topic><topic>synaptic dysfunction</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Tao, Wenyuan</creatorcontrib><creatorcontrib>Yu, Linjie</creatorcontrib><creatorcontrib>Shu, Shu</creatorcontrib><creatorcontrib>Liu, Ying</creatorcontrib><creatorcontrib>Zhuang, Zi</creatorcontrib><creatorcontrib>Xu, Siyi</creatorcontrib><creatorcontrib>Bao, Xinyu</creatorcontrib><creatorcontrib>Gu, Yue</creatorcontrib><creatorcontrib>Cai, Fang</creatorcontrib><creatorcontrib>Song, Weihong</creatorcontrib><creatorcontrib>Xu, Yun</creatorcontrib><creatorcontrib>Zhu, Xiaolei</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Molecular therapy</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Tao, Wenyuan</au><au>Yu, Linjie</au><au>Shu, Shu</au><au>Liu, Ying</au><au>Zhuang, Zi</au><au>Xu, Siyi</au><au>Bao, Xinyu</au><au>Gu, Yue</au><au>Cai, Fang</au><au>Song, Weihong</au><au>Xu, Yun</au><au>Zhu, Xiaolei</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>miR-204-3p/Nox4 Mediates Memory Deficits in a Mouse Model of Alzheimer’s Disease</atitle><jtitle>Molecular therapy</jtitle><addtitle>Mol Ther</addtitle><date>2021-01-06</date><risdate>2021</risdate><volume>29</volume><issue>1</issue><spage>396</spage><epage>408</epage><pages>396-408</pages><issn>1525-0016</issn><eissn>1525-0024</eissn><abstract>Alzheimer’s disease (AD) is the most common neurodegenerative disorder leading to dementia in the elderly, and the mechanisms of AD are not fully defined. MicroRNAs (miRNAs) have been shown to contribute to memory deficits in AD. In this study, we identified that miR-204-3p was downregulated in the hippocampus and plasma of 6-month-old APPswe/PS1dE9 (APP/PS1) mice. miR-204-3p overexpression attenuated memory and synaptic deficits in APP/PS1 mice. The amyloid levels and oxidative stress were decreased in the hippocampus of APP/PS1 mice after miR-204-3p overexpression. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 4 (Nox4) was a target of miR-204-3p, and Nox4 inhibition by GLX351322 protected neuronal cells against Aβ1–42-induced neurotoxicity. Furthermore, GLX351322 treatment rescued synaptic and memory deficits, and decreased oxidative stress and amyloid levels in the hippocampus of APP/PS1 mice. These results revealed that miR-204-3p attenuated memory deficits and oxidative stress in APP/PS1 mice by targeting Nox4, and miR-204-3p overexpression and/or Nox4 inhibition might be a potential therapeutic strategy for AD treatment.
[Display omitted]
Zhu and colleagues demonstrate that miR-204-3p attenuates memory and synaptic deficits in APPswe/PS1dE9 (APP/PS1) mice via inhibition of NADPH oxidase 4 (Nox4). In addition, Nox4 inhibition by GLX351322 rescues memory deficits in APP/PS1 mice, suggesting that miR-204-3p overexpression and/or Nox4 inhibition is a potential therapeutic strategy for Alzheimer’s disease treatment.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>32950103</pmid><doi>10.1016/j.ymthe.2020.09.006</doi><tpages>13</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Alzheimer Disease - complications Alzheimer Disease - genetics Alzheimer’s disease Amyloid beta-Peptides - metabolism Animals beta amyloid Biomarkers Disease Models, Animal Disease Susceptibility memory deficits Memory Disorders - diagnosis Memory Disorders - etiology Mice Mice, Transgenic MicroRNAs - genetics miR-204-3p NADPH Oxidase 4 - genetics Nox4 Original Oxidative Stress synaptic dysfunction |
| title | miR-204-3p/Nox4 Mediates Memory Deficits in a Mouse Model of Alzheimer’s Disease |
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