Curcumin-Loaded Nanoparticles Potently Induce Adult Neurogenesis and Reverse Cognitive Deficits in Alzheimer’s Disease Model via Canonical Wnt/β-Catenin Pathway
Abstract
Neurogenesis, a process of generation of new neurons, is reported to be reduced in several neurodegenerative disorders including Alzheimer's disease (AD). Induction of neurogenesis by targeting endogenous neural stem cells (NSC) could be a promising therapeutic approach to such diseases by influencing the brain self-regenerative capacity. Curcumin, a neuroprotective agent, has poor brain bioavailability. Herein, we report that curcumin-encapsulated PLGA nanoparticles (Cur-PLGA-NPs) potently induce NSC proliferation and neuronal differentiation in vitro and in the hippocampus and subventricular zone of adult rats, as compared to uncoated bulk curcumin. Cur-PLGA-NPs induce neurogenesis by internalization into the hippocampal NSC. Cur-PLGA-NPs significantly increase expression of genes involved in cell proliferation (reelin, nestin, and Pax6) and neuronal differentiation (neurogenin, neuroD1, neuregulin, neuroligin, and Stat3). Curcumin nanoparticles increase neuronal differentiation by activating the Wnt/β-catenin pathway, involved in regulation of neurogenesis. These nanoparticles caused enhanced nuclear translocation of β-catenin, decreased GSK-3β levels, and increased promoter activity of the TCF/LEF and cyclin-D1. Pharmacological and siRNA-mediated genetic inhibition of the Wnt pathway blocked neurogenesis-stimulating effects of curcumin. These nanoparticles reverse learning and memory impairments in an amyloid beta induced rat model of AD-like phenotypes, by inducing neurogenesis. In silico molecular docking studies suggest that curcumin interacts with Wif-1, Dkk, and GSK-3β. These results suggest that curcumin nanoparticles induce adult neurogenesis through activation of the canonical Wnt/β-catenin pathway and may offer a therapeutic approach to treating neurodegenerative diseases such as AD, by enhancing a brain self-repair mechanism.
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In silico molecular docking studies found that Cur-PLGA-NPs induce neurogenesis through the canonical Wnt/β-catenin pathway.
“By in silico molecular docking studies it was found that these NPs induced neurogenesis through canonical Wnt/β-catenin pathway (Tiwari et al., 2013).”
From Nanotechnology: A Promising Approach for Delivery of Neuroprotective Drugs (2020) · cites this paper as Tiwari et al., 2013
Cur-PLGA-NPs produce better effect on impaired learning and memory parameters in an Aβ-induced rat model of AD.
“They produced better effect on impaired learning and memory parameters in an Aβ induced rat model of AD.”
From Nanotechnology: A Promising Approach for Delivery of Neuroprotective Drugs (2020) · cites this paper as Tiwari et al., 2013
Curcumin-encapsulated PLGA NPs (Cur-PLGA-NPs) have a better effect on neural stem cell proliferation and neuronal differentiation in vitro and in vivo compared to bulk curcumin.
“curcumin-encapsulated PLGA NPs (Cur-PLGA-NPs) demonstrated better effect on neural stem cell proliferation and neuronal differentiation in vitro as well as in vivo, as compared to bulk curcumin.”
From Nanotechnology: A Promising Approach for Delivery of Neuroprotective Drugs (2020) · cites this paper as Tiwari et al., 2013
Cur-PLGA-NPs significantly elevate expression of genes related to cell proliferation and neuronal differentiation in the hippocampal region.
“Cur-PLGA-NPs significantly elevated expression of genes related to cell proliferation and neuronal differentiation in hippocampal region.”
From Nanotechnology: A Promising Approach for Delivery of Neuroprotective Drugs (2020) · cites this paper as Tiwari et al., 2013
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- Authors
- Tiwari, S. K., Agarwal, S., Seth, B., Yadav, A., Nair, S., Bhatnagar, P., Karmakar, M., Kumari, M., Chauhan, L. K. S., Patel, D. K., Srivastava, V., Singh, D., Gupta, S. K., Tripathi, A., Chaturvedi, R. K., & Gupta, K. C.
- Affiliations
- Indian Institute of Toxicology Research (IN)
- Institute of Genomics and Integrative Biology (IN)
- Corresponding author
- Chaturvedi, Rajnish Kumar
- Gupta, Kailash Chand
- ORCID
- Venue
- ACS Nano
- Publisher
- American Chemical Society (ACS)
- Published
- 2013-12-10
- Volume
- 8
- Issue
- 1
- Pages
- 76-103
- ISSN
- 1936-0851 (ISSN-L)
- 1936-086X
- OpenAlex
- W2053374578
- Cited by
- 558
- References
- 94
- Citations by year
- 2026: 21 · 2025: 44 · 2024: 46 · 2023: 45 · 2022: 64 · 2021: 55 · 2020: 65 · 2019: 58 · 2018: 40 · 2017: 47 · 2016: 24 · 2015: 34 · 2014: 14
- FWCI
- 8.91
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- ACS Nano (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Council of Scientific and Industrial Research (Network projects BSC0103 and BSC0108)
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Curcumin's Biomedical Applications
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- curcumin, PLGA nanoparticles, adult neurogenesis, Alzheimer's disease, Wnt/β-catenin signaling, neural stem cells, neuronal differentiation, hippocampus, subventricular zone, amyloid-beta, learning and memory impairment, GSK3β, β-catenin nuclear translocation, WIF1, brain bioavailability, neurodegenerative disease treatment
- MeSH terms
- Reelin Protein, Alzheimer Disease, Animals, Cognition Disorders, Curcumin, Disease Models, Animal, Microscopy, Electron, Transmission, Wnt Proteins, beta Catenin, Rats, Nanoparticles
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