Fe65-engineered neuronal exosomes encapsulating corynoxine-B ameliorate cognition and pathology of Alzheimer’s disease
Open accessAbstract
Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by the predominant impairment of neurons in the hippocampus and the formation of amyloid plaques, hyperphosphorylated tau protein, and neurofibrillary tangles in the brain. The overexpression of amyloid-β precursor protein (APP) in an AD brain results in the binding of APP intracellular domain (AICD) to Fe65 protein via the C-terminal Fe65-PTB2 interaction, which then triggers the secretion of amyloid-β and the consequent pathogenesis of AD. Apparently, targeting the interaction between APP and Fe65 can offer a promising therapeutic approach for AD. Recently, exosome, a type of extracellular vesicle with diameter around 30–200 nm, has gained much attention as a potential delivery tool for brain diseases, including AD, due to their ability to cross the blood–brain barrier, their efficient uptake by autologous cells, and their ability to be surface-modified with target-specific receptor ligands. Here, the engineering of hippocampus neuron cell-derived exosomes to overexpress Fe65, enabled the development of a novel exosome-based targeted drug delivery system, which carried Corynoxine-B (Cory-B, an autophagy inducer) to the APP overexpressed-neuron cells in the brain of AD mice. The Fe65-engineered HT22 hippocampus neuron cell-derived exosomes (Fe65-EXO) loaded with Cory-B (Fe65-EXO-Cory-B) hijacked the signaling and blocked the natural interaction between Fe65 and APP, enabling APP-targeted delivery of Cory-B. Notably, Fe65-EXO-Cory-B induced autophagy in APP-expressing neuronal cells, leading to amelioration of the cognitive decline and pathogenesis in AD mice, demonstrating the potential of Fe65-EXO-Cory-B as an effective therapeutic intervention for AD.
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Iyaswamy et al. established an exosome-based targeted drug delivery system for Alzheimer's disease using Fe65-overexpressing hippocampus neuron cell-derived exosomes loaded with Corynoxine-B.
“Similarly, Iyaswamy et al. established a novel, exosome-based targeted drug delivery system for AD [243].”
From Extracellular vesicles as nanotheranostic platforms for targeted neurological disorder interventions (2024) · cites this paper as [243]
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- Authors
- Iyaswamy, A., Thakur, A., Guan, X.-J., Krishnamoorthi, S., Fung, T. Y., Lu, K., Gaurav, I., Yang, Z., Su, C.-F., Lau, K.-F., Zhang, K., Ng, R. C.-L., Lian, Q., Cheung, K.-H., Ye, K., Chen, H. J., & Li, M.
- Affiliations
- Hong Kong Baptist University (HK)
- University of Chicago (US)
- Chinese University of Hong Kong (HK)
- Manchester Academic Health Science Centre (GB)
- Guangzhou Women and Children Medical Center (CN)
- Chinese Academy of Sciences (CN)
- Corresponding author
- Iyaswamy, Ashok
- Thakur, Abhimanyu
- Chen, Huanhuan Joyce
- Li, Min
- ORCID
- Venue
- Signal Transduction and Targeted Therapy
- Published
- 2023-10-23
- Volume
- 8
- Issue
- 1
- Pages
- 404-404
- ISSN
- 2059-3635 (ISSN-L)
- PMC
- PMC10590775
- OpenAlex
- W4387857159
- Cited by
- 134
- References
- 50
- Citations by year
- 2026: 41 · 2025: 61 · 2024: 32
- FWCI
- 23.80
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Signal Transduction and Targeted Therapy (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Knowledge@UChicago (University of Chicago) (submittedVersion, cc-by-nc-nd)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Research Explorer (The University of Manchester) (submittedVersion, cc-by)
- University of Chicago (cc-by)
- Funders
- Cancer Research Foundation
- Lung Cancer Research Foundation
- University of Chicago
- Hong Kong Baptist University (IRCMS/19–20/H02, RC-IRCS-17-18/03, HKBU/RC-IRCs/17-18/03, HKBU-MPCF-003-2022-23)
- Health and Medical Research Fund (HMRF/17182551, 17182541, HMRF17182541, 17182551, 09203776)
- National Cancer Institute (R00CA226353, K99CA226353)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Keywords
- Alzheimer's disease, Fe65, amyloid precursor protein, exosome-based drug delivery, autophagy, hippocampal neurons, cognitive decline, amyloid plaques, tau hyperphosphorylation, extracellular vesicles
- MeSH terms
- Alzheimer Disease, Animals, Cognition, Indoles, Nerve Tissue Proteins, Neurons, Spiro Compounds, Amyloid beta-Protein Precursor, Mice, Exosomes
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