Role of non-coding RNAs in Alzheimer’s disease and treatment with traditional Chinese medicine

Abstract

BACKGROUND: The etiology of Alzheimer’s disease is diverse and its pathogenesis remains complex and incompletely understood. In recent years, non-coding RNAs have been demonstrated to play a key role in the regulation of amyloid-β abnormal deposition, tau hyperphosphorylation, neuroinflammation activation, mitochondrial dysfunction, and synaptic damage, offering new perspectives for elucidating mechanisms underlying diseases and development of drugs. Additionally, by regulating non-coding RNA networks, traditional Chinese medicine exhibits the advantages of multi-pathway intervention. OBJECTIVE: To review recent studies on the role of regulatory non-coding RNAs and transfer RNAs in the pathological mechanisms of Alzheimer’s disease, summarize the current status of traditional Chinese medicine monomers, compound formulas, and acupuncture in regulating different non-coding RNAs to exert anti-Alzheimer’s disease effects, and provide theoretical basis and direction reference for future optimization of clinical treatment strategies and development of novel drugs. METHODS: Using Chinese and English search terms including 'non-coding RNA, microRNA, long non-coding RNA, circular RNA, transfer RNA, Alzheimer’s disease, traditional Chinese medicine', relevant literature published from January 2015 to July 2025 was retrieved from CNKI and PubMed databases. According to inclusion and exclusion criteria, 101 articles were finally included for review. RESULTS AND CONCLUSION: (1) The occurrence and development of Alzheimer’s disease originate from a multifactorial interrelated pathological network, mainly including amyloid-β deposition, tau hyperphosphorylation, neuroinflammation activation, mitochondrial dysfunction, oxidative stress, synaptic structural and functional abnormalities, and calcium homeostasis imbalance, which can also interweave and synergistically promote disease progression. (2) Various regulatory non-coding RNAs such as microRNAs, long non-coding RNAs, circular RNAs, and transfer RNAs among housekeeping non-coding RNAs can regulate the above pathological processes at different levels, thereby affecting disease progression. (3) Many active components of traditional Chinese medicine monomers such as berberine, catalpol, Panax notoginseng saponins, ginsenoside Rg1, β-asarone, triptolide, and tanshinone IIA; traditional Chinese medicine compound formulas such as Anshen Dingzhi Formula, Tiaoxin Formula, Bushen Tiansui Formula; and acupuncture and moxibustion can upregulate or downregulate specific non-coding RNAs to intervene in multiple pathological links of Alzheimer’s disease, exert neuroprotective effects, and delay the occurrence and development of the disease.

1. Introduction

Alzheimer’s disease is a progressive neurodegenerative disorder associated with brain aging. Its clinical course begins with early cognitive impairment centered on memory deficits, often accompanied by psychiatric symptoms such as anxiety, depression, and apathy. As the disease progresses, it gradually affects multiple cognitive domains including language, visuospatial, and executive functions, leading to loss of self-care ability. In advanced stages, severe psychiatric and behavioral abnormalities such as delusions, hallucinations, and irritability may appear, ultimately resulting in comprehensive functional decline [1-2]. The main pathological hallmarks are extracellular deposition of β-amyloid protein and neurofibrillary tangles formed by hyperphosphorylated tau protein within neurons [3].

Despite extensive research on the pathology and pharmacological treatment of Alzheimer’s disease, the outcomes remain far below expectations [4-6]. Current therapeutic strategies, including neurotransmitter modulators and immunotherapies, can improve symptoms and quality of life to some extent, but have not yet achieved a cure or effectively halted cognitive decline [7]. Therefore, there is an urgent need to develop novel diagnostic and therapeutic approaches for Alzheimer’s disease.

Non-coding RNAs (ncRNAs) are RNA molecules that do not encode proteins or peptides. They are broadly classified into two categories: regulatory non-coding RNAs, such as microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), which primarily participate in gene expression regulation; and housekeeping non-coding RNAs, such as transfer RNAs (tRNAs), which are constitutively expressed and perform fundamental biological functions [8]. In recent years, with the rapid development of bioinformatics and high-throughput sequencing technologies, a large number of non-coding RNAs have been found to be enriched in a tissue-specific manner in the central nervous system, and their aberrant expression profiles are significantly associated with brain aging and the occurrence and development of neurodegenerative diseases.