Cannabidiol Promotes Amyloid Precursor Protein Ubiquitination and Reduction of Beta Amyloid Expression in SHSY5YAPP+ Cells Through PPARγ Involvement
Abstract
The amyloidogenic cascade is regarded as a key factor at the basis of Alzheimer's disease (AD) pathogenesis. The aberrant cleavage of amyloid precursor protein (APP) induces an increased production and a subsequent aggregation of beta amyloid (Aβ) peptide in limbic and association cortices. As a result, altered neuronal homeostasis and oxidative injury provoke tangle formation with consequent neuronal loss. Cannabidiol (CBD), a Cannabis derivative devoid of psychotropic effects, has attracted much attention because it may beneficially interfere with several Aβ-triggered neurodegenerative pathways, even though the mechanism responsible for such actions remains unknown. In the present research, the role of CBD was investigated as a possible modulating compound of APP processing in SHSY5Y(APP+) neurons. In addition, the putative involvement of peroxisome proliferator-activated receptor-γ (PPARγ) was explored as a candidate molecular site responsible for CBD actions. Results indicated the CBD capability to induce the ubiquitination of APP protein which led to a substantial decrease in APP full length protein levels in SHSY5Y(APP+) with the consequent decrease in Aβ production. Moreover, CBD promoted an increased survival of SHSY5Y(APP+) neurons, by reducing their long-term apoptotic rate. Obtained results also showed that all, here observed, CBD effects were dependent on the selective activation of PPARγ.
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Natural products such as cannabidiol (CBD) and tetrahydrocannabinol (THC) have shown to be effective in vitro and in vivo.
“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 [185]
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- Authors
- Scuderi, C., Steardo, L., & Esposito, G.
- Affiliations
- Sapienza University of Rome (IT)
- Corresponding author
- Scuderi, Caterina
- Esposito, Giuseppe
- Venue
- Phytotherapy Research
- Publisher
- Wiley
- Published
- 2013-11-28
- Volume
- 28
- Issue
- 7
- Pages
- 1007-1013
- ISSN
- 0951-418X (ISSN-L)
- 1099-1573
- OpenAlex
- W1597614159
- Cited by
- 161
- References
- 28
- Citations by year
- 2026: 10 · 2025: 12 · 2024: 14 · 2023: 21 · 2022: 21 · 2021: 26 · 2020: 15 · 2019: 9 · 2018: 6 · 2017: 11 · 2016: 7 · 2015: 6 · 2014: 2
- FWCI
- 3.47
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Phytotherapy Research (publishedVersion)
- PubMed (publishedVersion)
- IRIS Research product catalog (Sapienza University of Rome) (submittedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
- Health Sciences › Medicine › Complementary and alternative medicine › Medicinal Plants and Neuroprotection
- Keywords
- cannabidiol, amyloid precursor protein, ubiquitination, amyloid-beta, PPARγ, Alzheimer's disease, SH-SY5Y cells, APP processing, neuronal apoptosis, neuroprotection, cannabis derivatives
- MeSH terms
- Alzheimer Disease, Cannabidiol, Cell Line, Humans, Neurons, Up-Regulation, Amyloid beta-Peptides, Amyloid beta-Protein Precursor, Apoptosis, PPAR gamma, Ubiquitination
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