The homeostasis balance of copper, as an essential trace element for life activities, is crucial for maintaining the normal function of cells. Cuproptosis, discovered in recent years, is a novel type of programmed cell death triggered by the accumulation of excessive copper ions in mitochondria. The core mechanism lies in that copper ions, after being reduced by ferridoxin (FDX1), directly target and induce the oligomerization of the acylated tricarboxylic acid (TCA) cycle enzyme, thereby triggering fatal protein toxic stress. This distinctive mechanism operates independently of other recognized pathways of cell death, offering a novel perspective for elucidating the pathological processes underlying various diseases. A review of pertinent research conducted over the past four years reveals that cuproptosis is not only significantly implicated in the onset, progression, and treatment resistance of tumors but is also intricately associated with diverse pathological processes, including neurodegenerative diseases, cardiovascular diseases, metabolic disorders, and immune abnormalities. This article conducts a multi-level summary from molecular mechanisms to physiological and pathological significance; deeply explores the interaction between cuproptosis and various subcellular structures, as well as their complex signal regulatory network; and systematically expounds the cutting-edge strategies for treating cuproptosis, including traditional copper chelating agents, ion carriers, and copper-based nanomedicines, with a particular focus on the latest progress in the field of natural product research. This review has systematically summarized the therapeutic potential demonstrated by numerous natural active ingredients when precisely regulating the cuproptosis pathway to provide a theoretical reference for future research in this field.

Alzheimer's disease (AD) and vascular dementia (VD) are the two most common forms of dementia, and they share common mechanisms, especially in regard to neurovascular dysfunction. There has been increasing evidence that the disruption of the neurovascular unit (NVU), which consists of endothelial cells, pericytes, astrocytes, microglia, neurons, and basement membrane, is one of the key early events in both AD and VD. The objective of this review is to summarize the structure and physiological function of the NVU, then discuss the pathological remodeling of the NVU in AD and VD and finally, show emerging evidence of multi-target approaches that restore the NVU and neurovascular protection. We begin with a description of the structure, and dietary regulatory roles of the NVU in cerebral homeostasis, especially related to Aβ, the blood-brain barrier (BBB), and neurovascular coupling (NVC). The NVU is then related to the pathological events that cause AD and VD, specifically to impaired Aβ clearance, inflammatory cascades, oxidative stress, and neurovascular uncoupling. Finally, the discussion focuses on a multi-target approach involving exercise, estrogen therapy, mesenchymal stem cells/exosomes, remote ischemic conditioning (RIC), and mindfulness meditation, and analyzes its implications for recovering NVU structure and function. We also discuss the concept of traditional Chinese medicine (TCM) approaches associated with NVU modulation with herbal formulas, traditional Chinese exercises and acupuncture, which has integrative pathways for MVU modulation. NVU dysfunction has a significant and converging impact on the development of both AD and VD. There is considerable support for multi-pathway neurovascular unit targeting, which should show a significant delay in cognitive decline. Incorporating multi-modal evidence from contemporary and traditional medical systems could offer new insights for individualized, neurovascular-targeted therapy for dementia.

Background: Alzheimer’s disease and related dementias (ADRD) significant global public health challenges, leading to severe disability in patients and placing a heavy burden on caregivers. However, epidemiological studies focusing on ADRD in specific regions remain limited. This study aims to comprehensively analyze and describe the current status and changing trends of ADRD in Non-High-income East Asia (NHIEA), Non-High-income Southeast Asia (NHISEA), and High-income Asia Pacific (HIAP), providing more detailed real-world data to inform policymaking.Methods: The data for ADRD used in this study were extracted from the 2021 Global Burden of Disease (GBD) database. We employed three major indicators of disease burden—prevalence, incidence, and years lived with disability (YLD)—and explored associated risk factors, further analyzing trends by age and sex. The results are presented as mean values with 95% uncertainty intervals (UIs). Additionally, we explored the differences between NHIEA, NHISEA, HIAP and other regions, as well as the potential associations between the disease burden of Alzheimer’s and other dementias and socioeconomic factors.Results: The findings indicate that the burden of dementia is rising in East and Southeast Asia, with women showing a higher burden across all indicators. Notably, in NHIEA, particularly in China, the burden of dementia has increased with the rising Social Demographic Index (SDI). China experienced a 27.3% increase in Alzheimer’s disease and other dementia ASYRs from 1990 to 2021, with a sharp 7.6% annual surge in 2021 alone, outpacing regional averages. Gender analysis revealed that women bear a disproportionate burden of Alzheimer’s disease and related dementias, especially after menopause, when the risk increases significantly. The study also identified smoking, high blood sugar, and high body mass index as important risk factors affecting the disease burden. The contribution of these risk factors varies across regions, genders, and age groups.Conclusion: The health burden of ADRD remains substantial, with distinct patterns observed across NHIEA, NHISEA, and HIAP, including regional variations in gender, age, and risk factors. These findings highlight the need for tailored approaches to allocate healthcare resources and implement appropriate control measures based on the specific conditions of each region to address this growing public health challenge. Future research should prioritize comparative analyses across continents and within regions to inform the development of more region-specific prevention strategies for ADRD.

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder marked by cognitive decline and neuronal loss. Multiple forms of programmed cell death (PCD)—including apoptosis, pyroptosis, ferroptosis, cuproptosis, and disulfidoptosis—contribute to its pathogenesis, regulated by protein families such as caspases, RIPKs, gasdermins, and ATGs. Plant metabolites widely distributed across medicinal plants and enriched in botanical drugs used in traditional Chinese medicine (TCM), such as alkaloids, flavonoids, saponins, and polysaccharides, have attracted increasing attention for their potential regulatory effects on these PCD pathways. These metabolites are not unique to TCM, but their prevalence in TCM prescriptions provides a valuable framework for pharmacological investigation. Their biological activities are often determined by structural features—for example, the isoquinoline scaffold of berberine enhances membrane permeability, facilitating neuroprotective actions. Despite substantial research, comprehensive summaries remain limited. This review systematically integrates progress from the past 2 decades on how plant metabolites, particularly those enriched in TCM botanical drugs, regulate PCD in AD, with the aim of clarifying pharmacological mechanisms and highlighting prospects for drug discovery and clinical translation.

Alzheimer's disease (AD) is an incurable neurodegenerative disease that has become one of the most important diseases threatening global public health security. Dihuang Yinzi (DHYZ) is a traditional Chinese medicine that has been widely used for the treatment of AD and has significant therapeutic effects, but its specific mechanism of action is still unclear.The aim of the study is to investigate the specific mechanism of DHYZ in treating AD based on brain metabolomics and network pharmacology. In this study, the classic APPswe/PS1E9 (APP/PS1) mice were selected as the AD animal model, and the mechanism of DHYZ was studied. The learning and memory ability of mice was detected by Y-maze test, and the ultrastructure of neural cells in the brain of the mice was observed by transmission electron microscope (TEM). Then, the mechanism of DHYZ intervention in AD was analyzed by constructing network pharmacology, and combined with brain metabolomics based on ultra performance liquid chromatography-mass spectrometry (UPLC-MS) to detect differential metabolic markers and their metabolic pathways. In addition, a joint analysis of differential metabolites and potential targets for DHYZ treatment of AD is conducted to deeply explore the relationship between key targets, differential metabolites, and metabolic pathways. After 30 days of DHYZ treatment, the spatial work and reference memory ability of APP/PS1 mice were significantly improved, the structure of mitochondria and synapses in the neurons of the brain were basically normal. 202 potential targets for DHYZ treatment of AD were screened through network pharmacology, and after enrichment analysis, these targets showed correlation with redox reactions, mitochondrial and synaptic functional pathways. And 7 differential metabolites were identified in brain metabolomics are Nicotinic acid, N-Formyl-L-glutamic acid, 5-(2-Hydroxyethyl)-4-methylthiazole, D-Gulono-1,4-lactone, Norepinephrine, 3-Methylotrophicacid, Palmitic acid. These differential metabolites mainly involve nicotinite and nicotinamide metabolism, pertussis, cAMP signaling pathway, cysteine and methionine metabolism. Notablely, through matching analysis of targets and metabolites, a total of 20 genes were found to match Nicotinic acid, 51 genes were found to match norepinephrine, and 14 genes intersected with the two metabolites, enrichment analysis of the intersected genes showed that neuroactive light receptor interaction, serotonergic synapse, and cAMP signaling were significantly affected, which is consistent with previous network pharmacology results. This study identified the main chemical ingredients of DHYZ intervention in AD may originated from Polygala tenuifolia Wild, Dendrobium nobile Line and Ophiogon japonicus (L.f) Ker-Gawl. Combined with Y Maze, TEM and brain metabolomics, revealed that DHYZ can improve the learning and memory abilities and brain pathological morphology of APP/PS1 mice by regulating nicotinic acid, 3-Methylthiopropionic acid, pertussis and their metabolic pathways, including nicotinate and nicotinamide metabolism, cAMP signaling pathway and cysteine and methionine metabolism. In short, this study provides a new research foundation and direction for the treatment of AD with traditional Chinese medicine.