Basic Study
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Psychiatry. Apr 19, 2024; 14(4): 563-581
Published online Apr 19, 2024. doi: 10.5498/wjp.v14.i4.563
Tanshinone IIA improves Alzheimer’s disease via RNA nuclear-enriched abundant transcript 1/microRNA-291a-3p/member RAS oncogene family Rab22a axis
Long-Xiu Yang, Man Luo, Sheng-Yu Li
Long-Xiu Yang, Man Luo, Sheng-Yu Li, Department of Neurology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530000, Guangxi Zhuang Autonomous Region, China
Sheng-Yu Li, Department of Neurology, Wuming Hospital of Guangxi Medical University, Nanning 530199, Guangxi Zhuang Autonomous Region, China
Author contributions: Yang LX, Luo M, and Li SY contributed to the study design, experiments, data collection, and manuscript writing; Luo M and Li SY contributed to the visualization; Li SY contributed to the resources; and all authors have read and approved the final manuscript.
Supported by 2020 Guangxi Zhuang Autonomous Region Health Care Commission Self-Financing Research Projects, No. Z20200096; 2023 Guangxi University Young and Middle-Aged Teachers’ Basic Research Ability Improvement Project, No. 2023KY0091; National Natural Science Foundation of China, No. 82260241; and the Natural Science Foundation of Guangxi Province, No. 2015GXNSFAA139171 and No. 2020GXNSFAA259053.
Institutional animal care and use committee statement: All procedures involving animals were approved by the Animal Care and Use Committee of the First Affiliated Hospital of Guangxi Medical University, No. 2021(KY-E-292), and performed in accordance with the Guide for the Care and Use of Laboratory Animals. All surgery and euthanasia were performed under sodium pentobarbital anesthesia (200 mg/kg) by intraperitoneal injection, and all efforts were made to minimize suffering.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: The datasets used and/or analyzed in the current study are available from the corresponding author upon reasonable request.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Sheng-Yu Li, MD, Doctor, Teacher, Department of Neurology, The First Affiliated Hospital of Guangxi Medical University, No. 6 Shuangyong Road, Qingxiu District, Nanning 530000, Guangxi Zhuang Autonomous Region, China. 15177821212@163.com
Received: October 11, 2023
Peer-review started: October 11, 2023
First decision: December 26, 2023
Revised: January 9, 2024
Accepted: February 28, 2024
Article in press: February 28, 2024
Published online: April 19, 2024
ARTICLE HIGHLIGHTS
Research background

Alzheimer’s disease (AD) is a prevalent neurodegenerative disorder characterized by cognitive decline and neuronal loss. Oxidative stress and neuroinflammation play pivotal roles in the pathogenesis of this disease. Tanshinone IIA (Tan-IIA), which is derived from Salvia miltiorrhiza, shows potential neuroprotective effects. Understanding the molecular mechanisms underlying these effects is crucial for the development of novel therapeutic strategies.

Research motivation

The motivation for this study was to elucidate the mechanisms by which Tan-IIA exerts neuroprotective effects in AD, focusing on the potential modulation of the long non-coding RNA (lncRNA) nuclear enriched abundant transcript 1 (NEAT1), microRNA (miR)-291a-3p, and RAB22A, member of the RAS oncogene family (Rab22a) signaling pathways. This has important implications for the development of new AD therapies.

Research objectives

The objective of this study was to investigate the neuroprotective effects of Tan-IIA in AD models and elucidate the underlying molecular mechanisms. Specifically, we aimed to determine how Tan-IIA affects oxidative stress, neuroinflammation, and neuronal viability through the NEAT1/miR-291a-3p/Rab22a signaling axis.

Research methods

The study employed both in vivo and in vitro models of AD using mice and neural stem cells, respectively. Methods included histopathological examinations, enzyme-linked immunosorbent assays, western blotting, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays, reverse transcription quantitative polymerase chain reaction assays, and various molecular biology techniques to elucidate the role of the NEAT1/miR-291 a-3p/Rab22a pathway in mediating the effects of Tan-IIA.

Research results

Tan-IIA ameliorated AD-related pathological changes, reduced oxidative stress, and attenuated neuroinflammation in the mouse models. It modulated the expression of NEAT1, miR-291a-3p, and Rab22a, indicating the involvement of this signaling axis in its neuroprotective effects. This is the first study to link the amelioration of AD symptoms by Tan-IIA with the downregulation of NEAT1.

Research conclusions

Tan-IIA has potential therapeutic roles in AD by attenuating oxidative stress and neuroinflammation, primarily through the NEAT1/miR-291a-3p/Rab22a signaling axis. This highlights the intricate molecular interplay involved in AD and identifies lncRNAs and miRNAs as potential therapeutic targets.

Research perspectives

Future research should focus on validating the identified therapeutic targets, namely miR-291a-3p and Rab22a, in clinical AD models. It is also crucial to explore other potential molecular pathways affected by Tan-IIA to fully understand its neuroprotective mechanisms. Clinical trials are essential to determine the efficacy and safety of Tan-IIA-based therapies in patients with AD. Expanding our understanding of the role of NEAT1 in AD could open new avenues for RNA-based therapeutic strategies.