Curcumin-primed exosomes potently ameliorate cognitive function in AD mice by inhibiting hyperphosphorylation of the Tau protein through the AKT/GSK-3β pathway
Abstract
Alzheimer's disease (AD) is the progressive development of fatal neurodegenerative diseases. Owing to the unclearness of the pathogenesis of AD and the failure of the drug to cross the blood-brain barrier (BBB), there is currently a lack of effective diagnostic and therapeutic approaches in the treatment of AD. The aim of this study was to design exosomes (Exo) as a specifically designed carrier able to carry curcumin (cur) to prevent neuronal death in vitro and in vivo to alleviate the AD symptoms. Our results demonstrated that Exo improved the solubility and bioavailability of cur and increased drug penetration across the BBB by specific active targeting between Exo, inheriting the lymphocyte function-associated antigen 1 (LFA-1) and endothelial intercellular adhesion molecule 1 (ICAM-1). Exosomes derived from curcumin-treated (primed) cells (Exo-cur) can better prevent the death of neurons in vitro and in vivo to relieve the symptoms of AD by inhibiting phosphorylation of the Tau protein through activating the AKT/GSK-3β pathway. Our results suggested that Exo-cur featured highly effective BBB-crossing via receptor-mediated transcytosis to access brain tissues and inhibited Tau phosphorylation, holding great potential in improving targeted drug delivery and the recovery of neuronal function in AD therapy.
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Curcumin-loaded exosomes enhanced curcumin solubility, stability, and bioavailability, and curcumin exhibited a slow and smooth release profile.
“Moreover, it enhanced curcumin solubility, stability, and bioavailability, and curcumin exhibited a slow and smooth release profile.”
From Advances in Strategies to Transport Nanoparticles Across the Blood–Brain Barrier for Drug Delivery into the Brain for the Treatment of Alzheimer’s Disease (2026) · cites this paper as [116]
Curcumin-loaded exosomes showed enhanced brain penetration via receptor-mediated transport, with a 6.5 times higher brain concentration compared to free curcumin.
“Enhanced brain penetration via RMT was also observed, with a 6.5 times higher brain concentration compared to free curcumin.”
From Advances in Strategies to Transport Nanoparticles Across the Blood–Brain Barrier for Drug Delivery into the Brain for the Treatment of Alzheimer’s Disease (2026) · cites this paper as [116]
Curcumin-loaded exosomes inherited lymphocyte function-associated antigen 1 (LFA-1) from their parental cells, a protein that interacts with endothelial intercellular adhesion molecule 1 (ICAM-1) for BBB crossing.
“Western plot analysis confirmed the inheritance of lymphocyte function-associated antigen 1 (LFA-1) from their parental cells, a protein that interacts with the endothelial intercellular adhesion molecule 1 (ICAM-1), used for BBB crossing.”
From Advances in Strategies to Transport Nanoparticles Across the Blood–Brain Barrier for Drug Delivery into the Brain for the Treatment of Alzheimer’s Disease (2026) · cites this paper as [116]
No significant cytotoxicity was reported for curcumin-loaded exosomes; in vivo, higher hippocampus accumulation and a reduction in OA-induced neuronal injury, cytotoxicity, and tau phosphorylation were confirmed.
“No significant cytotoxicity was reported; in vivo, higher hippocampus accumulation was observed, and a reduction in OA-induced neuronal injury, cytotoxicity, and tau phosphorylation was confirmed.”
From Advances in Strategies to Transport Nanoparticles Across the Blood–Brain Barrier for Drug Delivery into the Brain for the Treatment of Alzheimer’s Disease (2026) · cites this paper as [116]
The MWM test revealed an amelioration of learning and memory abilities in curcumin-loaded exosome-treated animals.
“The MWM test revealed an amelioration of learning and memory abilities by presenting shorter escape latencies, spatially oriented swimming behavior, and more time in the targeted quadrant.”
From Advances in Strategies to Transport Nanoparticles Across the Blood–Brain Barrier for Drug Delivery into the Brain for the Treatment of Alzheimer’s Disease (2026) · cites this paper as [116]
Naïve exosomes also reduced OA-induced consequences and inhibited microglia activation and neuronal cell apoptosis.
“Finally, naïve exosomes also reduced OA-induced consequences and inhibited microglia activation and neuronal cell apoptosis.”
From Advances in Strategies to Transport Nanoparticles Across the Blood–Brain Barrier for Drug Delivery into the Brain for the Treatment of Alzheimer’s Disease (2026) · cites this paper as [116]
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- Authors
- Wang, H., Sui, H., Zheng, Y., Jiang, Y., Shi, Y., Liang, J., & Zhao, L.
- Affiliations
- Jinzhou Medical University (CN)
- Corresponding author
- Shi, Yijie
- Liang, Jia
- Zhao, Liang
- Venue
- Nanoscale
- Publisher
- Royal Society of Chemistry (RSC)
- Published
- 2019
- Volume
- 11
- Issue
- 15
- Pages
- 7481-7496
- ISSN
- 2040-3364 (ISSN-L)
- 2040-3372
- OpenAlex
- W2923362583
- Cited by
- 324
- References
- 48
- Citations by year
- 2026: 26 · 2025: 51 · 2024: 48 · 2023: 63 · 2022: 45 · 2021: 51 · 2020: 32 · 2019: 8
- FWCI
- 23.40
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Nanoscale (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (81501017, 81502484)
- Natural Science Foundation of Liaoning Province (201602337)
- Department of Education of Liaoning Province (JYTQN201719)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Curcumin's Biomedical Applications
- Keywords
- curcumin, exosomes, Alzheimer's disease, tau hyperphosphorylation, blood-brain barrier penetration, transcytosis, drug delivery, neuronal cell death, cognitive function
- MeSH terms
- RAW 264.7 Cells, Glycogen Synthase Kinase 3 beta, Alzheimer Disease, Animals, Cognition, Curcumin, Disease Models, Animal, Drug Carriers, Male, Phosphorylation, tau Proteins, Rats, Sprague-Dawley, Proto-Oncogene Proteins c-akt, Mice, Rats, Exosomes
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