Neuroprotection and Mechanism of Gas-miR36-5p from <i>Gastrodia elata</i> in an Alzheimer’s Disease Model by Regulating Glycogen Synthase Kinase-3β

Alzheimer’s disease (AD) is currently the most common neurodegenerative disease. Glycogen synthase kinase 3β (GSK-3β) is a pivotal factor in AD pathogenesis. Recent research has demonstrated that plant miRNAs exert cross-kingdom regulation on the target genes in animals. <i>Gastrodia elata<...

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Main Authors: Zhongteng Lu, Jianyuan Fu, Guang Wu, Zhecheng Yang, Xiaoqi Wu, Dan Wang, Zhengying You, Zuoming Nie, Qing Sheng
Format: Article
Language:English
Published: MDPI AG 2023-12-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/24/24/17295
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author Zhongteng Lu
Jianyuan Fu
Guang Wu
Zhecheng Yang
Xiaoqi Wu
Dan Wang
Zhengying You
Zuoming Nie
Qing Sheng
author_facet Zhongteng Lu
Jianyuan Fu
Guang Wu
Zhecheng Yang
Xiaoqi Wu
Dan Wang
Zhengying You
Zuoming Nie
Qing Sheng
author_sort Zhongteng Lu
collection DOAJ
description Alzheimer’s disease (AD) is currently the most common neurodegenerative disease. Glycogen synthase kinase 3β (GSK-3β) is a pivotal factor in AD pathogenesis. Recent research has demonstrated that plant miRNAs exert cross-kingdom regulation on the target genes in animals. <i>Gastrodia elata</i> (<i>G. elata</i>) is a valuable traditional Chinese medicine that has significant pharmacological activity against diseases of the central nervous system (CNS). Our previous studies have indicated that <i>G. elata</i>-specific miRNA plays a cross-kingdom regulatory role for the NF-<i>κ</i>B signaling pathway in mice. In this study, further bioinformatics analysis suggested that Gas-miR36-5p targets GSK-3β. Through western blot, RT-qPCR, and assessments of T-AOC, SOD, and MDA levels, Gas-miR36-5p demonstrated its neuroprotective effects in an AD cell model. Furthermore, Gas-miR36-5p was detected in the murine brain tissues. The results of the Morris water maze test and western blot analysis provided positive evidence for reversing the learning deficits and hyperphosphorylation of Tau in AD mice, elucidating significant neuroprotective effects in an AD model following <i>G. elata</i> RNA administration. Our research emphasizes Gas-miR36-5p as a novel <i>G. elata</i>-specific miRNA with neuroprotective properties in Alzheimer’s disease by targeting GSK-3β. Consequently, our findings provide valuable insights into the cross-kingdom regulatory mechanisms underlying <i>G. elata</i>-specific miRNA, presenting a novel perspective for the treatment of Alzheimer’s disease.
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spelling doaj.art-9226b7c694a64083b3ce7f4ce9fe247e2023-12-22T14:13:57ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-12-0124241729510.3390/ijms242417295Neuroprotection and Mechanism of Gas-miR36-5p from <i>Gastrodia elata</i> in an Alzheimer’s Disease Model by Regulating Glycogen Synthase Kinase-3βZhongteng Lu0Jianyuan Fu1Guang Wu2Zhecheng Yang3Xiaoqi Wu4Dan Wang5Zhengying You6Zuoming Nie7Qing Sheng8College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou 310018, ChinaCollege of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou 310018, ChinaCollege of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou 310018, ChinaCollege of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou 310018, ChinaCollege of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou 310018, ChinaCollege of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou 310018, ChinaCollege of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou 310018, ChinaCollege of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou 310018, ChinaCollege of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou 310018, ChinaAlzheimer’s disease (AD) is currently the most common neurodegenerative disease. Glycogen synthase kinase 3β (GSK-3β) is a pivotal factor in AD pathogenesis. Recent research has demonstrated that plant miRNAs exert cross-kingdom regulation on the target genes in animals. <i>Gastrodia elata</i> (<i>G. elata</i>) is a valuable traditional Chinese medicine that has significant pharmacological activity against diseases of the central nervous system (CNS). Our previous studies have indicated that <i>G. elata</i>-specific miRNA plays a cross-kingdom regulatory role for the NF-<i>κ</i>B signaling pathway in mice. In this study, further bioinformatics analysis suggested that Gas-miR36-5p targets GSK-3β. Through western blot, RT-qPCR, and assessments of T-AOC, SOD, and MDA levels, Gas-miR36-5p demonstrated its neuroprotective effects in an AD cell model. Furthermore, Gas-miR36-5p was detected in the murine brain tissues. The results of the Morris water maze test and western blot analysis provided positive evidence for reversing the learning deficits and hyperphosphorylation of Tau in AD mice, elucidating significant neuroprotective effects in an AD model following <i>G. elata</i> RNA administration. Our research emphasizes Gas-miR36-5p as a novel <i>G. elata</i>-specific miRNA with neuroprotective properties in Alzheimer’s disease by targeting GSK-3β. Consequently, our findings provide valuable insights into the cross-kingdom regulatory mechanisms underlying <i>G. elata</i>-specific miRNA, presenting a novel perspective for the treatment of Alzheimer’s disease.https://www.mdpi.com/1422-0067/24/24/17295Alzheimer’s diseaseGSK-3βhyperphosphorylation of tau protein<i>Gastrodia elata</i> miRNAGas-miR36-5pneuroprotection
spellingShingle Zhongteng Lu
Jianyuan Fu
Guang Wu
Zhecheng Yang
Xiaoqi Wu
Dan Wang
Zhengying You
Zuoming Nie
Qing Sheng
Neuroprotection and Mechanism of Gas-miR36-5p from <i>Gastrodia elata</i> in an Alzheimer’s Disease Model by Regulating Glycogen Synthase Kinase-3β
International Journal of Molecular Sciences
Alzheimer’s disease
GSK-3β
hyperphosphorylation of tau protein
<i>Gastrodia elata</i> miRNA
Gas-miR36-5p
neuroprotection
title Neuroprotection and Mechanism of Gas-miR36-5p from <i>Gastrodia elata</i> in an Alzheimer’s Disease Model by Regulating Glycogen Synthase Kinase-3β
title_full Neuroprotection and Mechanism of Gas-miR36-5p from <i>Gastrodia elata</i> in an Alzheimer’s Disease Model by Regulating Glycogen Synthase Kinase-3β
title_fullStr Neuroprotection and Mechanism of Gas-miR36-5p from <i>Gastrodia elata</i> in an Alzheimer’s Disease Model by Regulating Glycogen Synthase Kinase-3β
title_full_unstemmed Neuroprotection and Mechanism of Gas-miR36-5p from <i>Gastrodia elata</i> in an Alzheimer’s Disease Model by Regulating Glycogen Synthase Kinase-3β
title_short Neuroprotection and Mechanism of Gas-miR36-5p from <i>Gastrodia elata</i> in an Alzheimer’s Disease Model by Regulating Glycogen Synthase Kinase-3β
title_sort neuroprotection and mechanism of gas mir36 5p from i gastrodia elata i in an alzheimer s disease model by regulating glycogen synthase kinase 3β
topic Alzheimer’s disease
GSK-3β
hyperphosphorylation of tau protein
<i>Gastrodia elata</i> miRNA
Gas-miR36-5p
neuroprotection
url https://www.mdpi.com/1422-0067/24/24/17295
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