Effects of cannabidiol interactions with Wnt/β-catenin pathway and PPARγ on oxidative stress and neuroinflammation in Alzheimer's disease
Abstract
Alzheimer's disease (AD) is a neurodegenerative disease, in which the primary etiology remains unknown. AD presents amyloid beta (Aβ) protein aggregation and neurofibrillary plaque deposits. AD shows oxidative stress and chronic inflammation. In AD, canonical Wingless-Int (Wnt)/β-catenin pathway is downregulated, whereas peroxisome proliferator-activated receptor γ (PPARγ) is increased. Downregulation of Wnt/β-catenin, through activation of glycogen synthase kinase-3β (GSK-3β) by Aβ, and inactivation of phosphatidylinositol 3-kinase/Akt signaling involve oxidative stress in AD. Cannabidiol (CBD) is a non-psychotomimetic phytocannabinoid from Cannabis sativa plant. In PC12 cells, Aβ-induced tau protein hyperphosphorylation is inhibited by CBD. This inhibition is associated with a downregulation of p-GSK-3β, an inhibitor of Wnt pathway. CBD may also increase Wnt/β-catenin by stimulation of PPARγ, inhibition of Aβ and ubiquitination of amyloid precursor protein. CBD attenuates oxidative stress and diminishes mitochondrial dysfunction and reactive oxygen species generation. CBD suppresses, through activation of PPARγ, pro-inflammatory signaling and may be a potential new candidate for AD therapy.
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In PC12 neuronal cells, CBD has shown inhibition of tau hyperphosphorylation.
“In PC12 neuronal cells, CBD has shown protection against oxidative stress, Aβ-induced neurotoxicity, inhibition of tau hyperphosphorylation, prevention of proinflammatory gene transcription, and inhibition of Aβ-induced tau hyperphosphorylation [188,189].”
From The Multifaceted Role of Neuroprotective Plants in Alzheimer’s Disease Treatment (2022) · cites this paper as [188]
In PC12 neuronal cells, CBD has shown protection against oxidative stress and Aβ-induced neurotoxicity.
“In PC12 neuronal cells, CBD has shown protection against oxidative stress, Aβ-induced neurotoxicity, inhibition of tau hyperphosphorylation, prevention of proinflammatory gene transcription, and inhibition of Aβ-induced tau hyperphosphorylation [188,189].”
From The Multifaceted Role of Neuroprotective Plants in Alzheimer’s Disease Treatment (2022) · cites this paper as [188]
In PC12 neuronal cells, CBD has shown prevention of proinflammatory gene transcription.
“In PC12 neuronal cells, CBD has shown protection against oxidative stress, Aβ-induced neurotoxicity, inhibition of tau hyperphosphorylation, prevention of proinflammatory gene transcription, and inhibition of Aβ-induced tau hyperphosphorylation [188,189].”
From The Multifaceted Role of Neuroprotective Plants in Alzheimer’s Disease Treatment (2022) · cites this paper as [188]
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Alzheimer’s Disease and Protein Kinases
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Adverse Impact of Cannabis on Human Health
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PPAR Gamma and Viral Infections of the Brain
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Is cannabidiol a drug acting on unconventional targets to control drug‐resistant epilepsy?
Rocha, L., Frías‐Soria, C. L., Ortíz, J. G., Auzmendi, J., & Lazarowski, A. (2020) · Epilepsia Open · doi:10.1002/epi4.12376 · Cited by 26 · see citing works
The role of Wnt/mTOR signaling in spinal cord injury
Peng, C. M., Liao, H.-Y., & Zhang, H. (2022) · Journal of Clinical Orthopaedics and Trauma · doi:10.1016/j.jcot.2022.101760 · Cited by 23 · see citing works
Reece, A. S., & Hulse, G. K. (2022) · Archives of Public Health · doi:10.1186/s13690-022-00812-7 · Cited by 24 · see citing works
Characterization of the biochemical and behavioral effects of cannabidiol: implications for migraine
Greco, R., Francavilla, M., Demartini, C., Zanaboni, A. M., Sodergren, M. H., Facchetti, S., Pacchetti, B., Palmisani, M., Franco, V., & Tassorelli, C. (2023) · The Journal of Headache and Pain · doi:10.1186/s10194-023-01589-y · Cited by 25 · see citing works
- Authors
- Vallée, A., Lecarpentier, Y., Guillevin, R., & Vallée, J.-N.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- Venue
- Acta Biochimica et Biophysica Sinica
- Published
- 2017-10-01
- Volume
- 49
- Issue
- 10
- Pages
- 853-866
- ISSN
- 1672-9145 (ISSN-L)
- OpenAlex
- W2738129635
- Cited by
- 226
- References
- 244
- Citations by year
- 2026: 20 · 2025: 17 · 2024: 26 · 2023: 29 · 2022: 37 · 2021: 37 · 2020: 31 · 2019: 16 · 2018: 9 · 2017: 4
- FWCI
- 12.18
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Acta Biochimica et Biophysica Sinica (publishedVersion)
- PubMed (publishedVersion)
- 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, Alzheimer's disease, Wnt/β-catenin signaling, PPARγ, oxidative stress, neuroinflammation, amyloid-beta, glycogen synthase kinase-3β, tau hyperphosphorylation, phosphatidylinositol 3-kinase/Akt signaling, mitochondrial dysfunction, reactive oxygen species, neuroprotection
- MeSH terms
- Glycogen Synthase Kinase 3 beta, Alzheimer Disease, Animals, Cannabidiol, Inflammation, Models, Biological, Phosphorylation, Amyloid beta-Peptides, PC12 Cells, Neurofibrillary Tangles, tau Proteins, Oxidative Stress, PPAR gamma, Rats, Wnt Signaling Pathway
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