Key Takeaways & Executive Findings
- •• SIRT1 signaling pathway plays a crucial role in Alzheimer's disease by regulating energy metabolism, oxidative stress, neuroinflammation, autophagy, and apoptosis. • Traditional Chinese medicine monomers and compounds can activate SIRT1 signaling to protect neurons and delay AD progression. • Sodium ferulate improves cognitive function in AD rats by upregulating SIRT1 expression in the prefrontal cortex. • Oyster peptide alleviates oxidative damage and neuroinflammation in the hippocampus, enhancing synaptic function and neuronal survival.
Abstract
BACKGROUND: Silent information regulator 1, as a deacetylase, can regulate the transcriptional activity of various proteins and many Alzheimer’s disease related pathological processes after activation, including regulating energy metabolism, oxidative stress, neuroinflammation, autophagy, and cell apoptosis. It is closely related to the occurrence, development, and prognosis of Alzheimer’s disease. In recent years, a large number of studies have found that the active ingredients and formulas of traditional Chinese medicine monomers can delay the development of Alzheimer's disease by activating the silent information regulator 1 signaling pathway, reducing cell apoptosis, protecting neurons, and inhibiting the formation of amyloid plaque. OBJECTIVE: To explore the relationship between silent information regulator 1 and Alzheimer’s disease, as well as the action mechanism of traditional Chinese medicine in regulating the silent information regulator 1 signaling pathway for the treatment of Alzheimer’s disease. METHODS: The CNKI, WanFang, VIP, SinoMed, and PubMed databases were searched for literature published from January 2015 to March 2025 using Chinese and English search terms including 'Alzheimer’s disease, dementia, SIRT1, inflammation, oxidative stress, inflammatory factors, signaling pathways, TCM monomers, compounds'. A total of 4,921 relevant articles were retrieved, and 154 were finally included for review. RESULTS AND CONCLUSION: A large number of experimental studies have confirmed that silent information regulator 1 plays an important role in Alzheimer’s disease. Traditional Chinese medicine formulas can regulate the silent information regulator 1 signaling pathway in various ways. For example, sodium ferulate improves the learning and memory ability of Alzheimer’s disease rats by increasing the expression of silent information regulator 1 in the prefrontal cortex, thereby ameliorating nerve cell damage caused by ischemia and hypoxia. Oyster peptide can enhance reactive oxygen species, reduce oxidative damage in hippocampal tissue, alleviate neuroinflammation, enhance synaptic function, reduce neuronal damage and death, exert brain protective effects, and improve cognitive dysfunction.
1. Introduction
Alzheimer's disease is a common neurodegenerative disease [1]. Its pathogenesis is a complex network of multiple factors, in which inflammatory response, energy metabolism disorder, oxidative stress, autophagy, and apoptosis together constitute the core pathological axis of neurodegeneration, and through complex molecular interactions synergistically aggravate β-amyloid deposition and tau protein pathology, forming a vicious cycle [2-3]. Currently, the treatment of Alzheimer's disease mainly focuses on 'anti-β-amyloid and anti-tau', but it still faces challenges such as low response rate to targeted therapy and limited symptom improvement. Therefore, it is necessary to reveal deeper pathological mechanisms and develop more effective therapeutic targets.
Silent information regulator 1 (SIRT1), as a nicotinamide adenine dinucleotide-dependent deacetylase, regulates the expression of various proteins through its deacetylase activity, thereby exerting multiple protective effects in Alzheimer's disease. Studies have shown that SIRT1 can improve the chronic neuroinflammatory microenvironment in Alzheimer's disease [4], promote mitochondrial biogenesis and reduce reactive oxygen species accumulation [5], and activate autophagy-related proteins [6], thereby accelerating the degradation of β-amyloid aggregates and abnormal tau protein, ultimately improving synaptic plasticity and memory function. Based on these findings, targeting SIRT1 to regulate oxidative stress, inflammatory response, autophagy, and energy metabolism [7] may provide new intervention strategies for the clinical treatment of Alzheimer's disease.
In recent years, traditional Chinese medicine has achieved excellent results in the prevention and treatment of Alzheimer's disease. A large number of studies have shown that traditional Chinese medicine can significantly enhance neuronal activity, effectively inhibit abnormal aggregation of β-amyloid, and regulate tau protein phosphorylation levels by activating the SIRT1 signaling pathway, thereby achieving therapeutic effects on Alzheimer's disease. However, there is a lack of relevant reviews on this topic. In view of this, this article conducted a literature search in CNKI, WanFang, VIP, SinoMed, PubMed and other databases, starting from SIRT1 to briefly introduce its basic functions, elaborate the role of SIRT1 signaling pathway in the pathogenesis of Alzheimer's disease, and systematically summarize the regulation of SIRT1 by traditional Chinese medicine.
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Zhao Fangfang, Guo Yanke, Wang Xueke, Pang Botong, Zhu Yanqiang, Qin Yang, Cui Yinglin (2026). A new approach to intervene in Alzheimer's disease through regulating the silencing information regulator 1 signaling pathway with traditional Chinese medicine. Chinese Journal of Tissue Engineering Research. https://doi.org/10.12307/2026.21541
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Frequently Asked Questions
What is the role of SIRT1 in Alzheimer's disease?
SIRT1, as a deacetylase, regulates various proteins involved in energy metabolism, oxidative stress, neuroinflammation, autophagy, and apoptosis. Activation of SIRT1 has been shown to protect neurons, reduce amyloid plaque formation, and improve cognitive function in Alzheimer's disease models.
How does traditional Chinese medicine regulate SIRT1 signaling pathway?
Traditional Chinese medicine monomers and compounds can activate the SIRT1 signaling pathway through various mechanisms, such as increasing SIRT1 expression, enhancing its deacetylase activity, and modulating downstream targets, thereby exerting neuroprotective effects in Alzheimer's disease.
What are the key findings of this review?
The review summarizes that SIRT1 plays a crucial role in Alzheimer's disease, and traditional Chinese medicine can regulate SIRT1 signaling to protect neurons by modulating energy homeostasis, oxidative stress, neuroinflammation, and synaptic plasticity. Specific examples include sodium ferulate and oyster peptide.
What is the significance of this review?
This review provides a comprehensive summary of the current research on SIRT1 and traditional Chinese medicine in Alzheimer's disease, highlighting potential therapeutic targets and mechanisms, which may guide future drug development and clinical applications.
What are the limitations of current research?
The review notes that although many studies have demonstrated the beneficial effects of traditional Chinese medicine on SIRT1 signaling, there is a lack of clinical trials and standardized protocols. Further research is needed to translate these findings into clinical practice.
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