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Cannabidiol Reduces Aβ-Induced Neuroinflammation and Promotes Hippocampal Neurogenesis through PPARγ Involvement
Open accessAbstract
Peroxisome proliferator-activated receptor-γ (PPARγ) has been reported to be involved in the etiology of pathological features of Alzheimer's disease (AD). Cannabidiol (CBD), a Cannabis derivative devoid of psychomimetic effects, has attracted much attention because of its promising neuroprotective properties in rat AD models, even though the mechanism responsible for such actions remains unknown. This study was aimed at exploring whether CBD effects could be subordinate to its activity at PPARγ, which has been recently indicated as its putative binding site. CBD actions on β-amyloid-induced neurotoxicity in rat AD models, either in presence or absence of PPAR antagonists were investigated. Results showed that the blockade of PPARγ was able to significantly blunt CBD effects on reactive gliosis and subsequently on neuronal damage. Moreover, due to its interaction at PPARγ, CBD was observed to stimulate hippocampal neurogenesis. All these findings report the inescapable role of this receptor in mediating CBD actions, here reported.
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“CBD decreases the neuronal damage induced by β-amyloid protein deposit (105); (114–116)”
From Translational investigation of the therapeutic potential of Cannabidiol (CBD): Toward a new age (2018) · cites this paper as [105]
In the citing paper
“CBD (administered intraperitoneally during 15 days) prevented the neurogenic disruption observed in a genetic murine model of Alzheimer's Disease through a peroxisome proliferator-activated receptor γ (PPARγ)-dependent mechanism (105).”
From Translational investigation of the therapeutic potential of Cannabidiol (CBD): Toward a new age (2018) · cites this paper as [105]
In the citing paper
“In vivo, CBD has shown attenuation of Aβ-induced neuroinflammatory responses by minimizing proinflammatory gene and mediator expression, as well as minimized reactive gliosis [187,190].”
From The Multifaceted Role of Neuroprotective Plants in Alzheimer’s Disease Treatment (2022) · cites this paper as [187]
In the citing paper
“In vivo, CBD has shown attenuation of Aβ-induced neuroinflammatory responses by minimizing proinflammatory gene and mediator expression, as well as minimized reactive gliosis [187,190].”
From The Multifaceted Role of Neuroprotective Plants in Alzheimer’s Disease Treatment (2022) · cites this paper as [187]
In the citing paper
“Consequently, natural products, such as cannabidiol (CBD) and tetrahydrocannabinol (THC), have also shown to be effective in vitro and in vivo [184,185,186,187].”
From The Multifaceted Role of Neuroprotective Plants in Alzheimer’s Disease Treatment (2022) · cites this paper as [187]
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Metadata
- Authors
- Esposito, G., Scuderi, C., Valenza, M., Togna, G. I., Latina, V., De Filippis, D., Cipriano, M., Carratù, M. R., Iuvone, T., & Steardo, L.
- Affiliations
- Sapienza University of Rome (IT)
- University of Bari Aldo Moro (IT)
- University of Naples Federico II (IT)
- Corresponding author
- Steardo, Luca
- ORCID
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2011-12-05
- Volume
- 6
- Issue
- 12
- Pages
- e28668
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC3230631
- OpenAlex
- W2107076749
- Cited by
- 410
- References
- 41
- Citations by year
- 2026: 23 · 2025: 24 · 2024: 53 · 2023: 41 · 2022: 49 · 2021: 48 · 2020: 45 · 2019: 22 · 2018: 18 · 2017: 26 · 2016: 16 · 2015: 13 · 2014: 8 · 2013: 13 · 2012: 10
- FWCI
- 7.26
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- IRIS Research product catalog (Sapienza University of Rome) (submittedVersion)
- CINECA IRIS Institutional Research Information System (University of Bari Aldo Moro) (submittedVersion)
- Funders
- Ministero dell’Istruzione, dell’Università e della Ricerca
- Topics
- Health Sciences › Medicine › Pharmacology (medical) › Cannabis and Cannabinoid Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- cannabidiol, PPARγ, Alzheimer's disease, amyloid-beta, neuroinflammation, hippocampal neurogenesis, reactive gliosis, neuroprotection, PPARγ antagonist, neurotoxicity
- MeSH terms
- Animals, Astrocytes, Binding Sites, Brain, Cannabidiol, Hippocampus, Inflammation, Male, Neurons, Nitric Oxide, Protein Binding, Time Factors, Amyloid beta-Peptides, Rats, Sprague-Dawley, Protein Structure, Tertiary, PPAR gamma, Rats, Neurogenesis
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