Study on the Pharmacological Efficacy and Mechanism of Dual-Target Liposome Complex AD808 Against Alzheimer’s Disease
Abstract
1. Introduction
2. Results
2.1. Characterization of AD808 Liposomal Complex
2.2. Evaluation of Blood–Brain Barrier Permeability
2.3. AD808 Ameliorates Cognitive Deficits in AD Mice
2.4. AD808 Improves the Pathomorphology of the Hippocampus in Alzheimer’s Disease (AD) Mice
2.5. AD808 Reduced Neuronal Apoptosis in Alzheimer’s Disease (AD) Mice
2.6. AD808 Reduced Amyloid Plaque Burden in Alzheimer’s Disease (AD) Mouse Brains
2.7. AD808 Ameliorates Neuroinflammation in Alzheimer’s Disease (AD) Mice
2.8. AD808 Can Transform M1-Polarized Microglia into the M2 Phenotype
2.9. AD808 Promotes the Expression of Neurotrophic Factors in the Brain Tissue of Alzheimer’s Disease (AD) Mice
2.10. AD808 Increases MT3 Protein Levels in Brain Tissue
2.11. AD808 Upregulates TREM2 Expression in Brain Tissue
2.12. AD808-Mediated Neural Repair via the STING/IRF3 and PI3K/AKT Pathways
3. Discussion
Pharmacological Mechanism of AD808 in the Treatment of Alzheimer’s Disease
4. Materials and Methods
4.1. Materials
4.2. Preparation of AD808 Liposomal Complex
4.3. Characterization of AD808 Liposomal Complex
4.4. Establishment of In Vitro Blood–Brain Barrier Model and Evaluation of AD808 Permeability
4.5. 15N Stable Isotope Ratio Analysis
4.6. The APP/PS1 Mouse Model
4.7. Grouping and Treatment Protocol for Mouse Models
4.8. Assessment of Cognitive and Memory Functions in Mice
4.9. Hematoxylin and Eosin (H&E) Staining
4.10. Cresyl Violet Staining for Nissl Granules
4.11. TUNEL Assay of Neuron Apoptosis
4.12. Aβ Plaque Histology
4.13. Biochemical Detection of Inflammatory Factors, Neurotrophic Factors, and Marker Aβ in AD Mouse Tissue
4.14. Identification and Characterization of Microglial Subtypes in AD Mouse Tissue
4.15. Immunofluorescence Analysis of the MT3, TREM2, STING/IRF3, and PI3K/AKT Pathways in Brain Tissue
4.16. Data Analysis
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
HSPC | Hydrogenated soybean phosphatidylcholine |
CHO | Cholesterol |
DSPE-PEG2000 | Phospholipid-methoxy polyethylene glycol |
DSPE-PEG2000-Mal | Maleimide-phospholipid-methoxy polyethylene glycol |
Aβ | β-amyloid |
TGF-β | Transforming growth factor-β |
MCP-1 | Monocyte chemoattractant protein-1 |
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Type | Size (nm) | Zeta (mv) | PDI | EE (%) | DL (%) | Protein Content (μg/mL) |
---|---|---|---|---|---|---|
Lip-blank | 182.6 ± 0.6 | −0.43 ± 1.2 | 0.114 | |||
AD808 | 198.1 ± 1.2 | −8.1 ± 4.9 | 0.119 | 88.7 ± 5.3 | 8.8 ± 0.1 | 231.4 ± 16.5 |
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Liu, C.; Wang, X.; Xu, W.; Yu, S.; Zhang, Y.; Xu, Q.; Tan, X. Study on the Pharmacological Efficacy and Mechanism of Dual-Target Liposome Complex AD808 Against Alzheimer’s Disease. Pharmaceuticals 2025, 18, 977. https://doi.org/10.3390/ph18070977
Liu C, Wang X, Xu W, Yu S, Zhang Y, Xu Q, Tan X. Study on the Pharmacological Efficacy and Mechanism of Dual-Target Liposome Complex AD808 Against Alzheimer’s Disease. Pharmaceuticals. 2025; 18(7):977. https://doi.org/10.3390/ph18070977
Chicago/Turabian StyleLiu, Chang, Xiaoqing Wang, Wei Xu, Songli Yu, Yueru Zhang, Qiming Xu, and Xiangshi Tan. 2025. "Study on the Pharmacological Efficacy and Mechanism of Dual-Target Liposome Complex AD808 Against Alzheimer’s Disease" Pharmaceuticals 18, no. 7: 977. https://doi.org/10.3390/ph18070977
APA StyleLiu, C., Wang, X., Xu, W., Yu, S., Zhang, Y., Xu, Q., & Tan, X. (2025). Study on the Pharmacological Efficacy and Mechanism of Dual-Target Liposome Complex AD808 Against Alzheimer’s Disease. Pharmaceuticals, 18(7), 977. https://doi.org/10.3390/ph18070977