Cannabidiol induces autophagy via CB₁ receptor and reduces α-synuclein cytosolic levels

Author(s)

Erustes, Adolfo G. ; Abilio, Vanessa C. ; Bincoletto, Claudia ; Piacentini, Mauro ; Pereira, Gustavo J. S. ; Smaili, Soraya S.

• Document type: Journal article
• Source: Brain Research; v. 1850, p. 10-pg., 2024-12-24.

Abstract

Numerous studies have explored the role of cannabinoids in neurological conditions, chronic pain and neurodegenerative diseases. Restoring autophagy has been proposed as a potential target for the treatment of neurodegenerative diseases. In our study, we used a neuroblastoma cell line that overexpresses wild-type alpha-synuclein to investigate the effects of cannabidiol on autophagy modulation and reduction in the level of cytosolic alpha-synuclein. Our results demonstrated that cannabidiol enhances the accumulation of LC3-II- and GFP-LC3-positive vesicles, which indicates an increase in autophagic flux. In addition, cannabidiol-treated cells showed a reduction in cytosolic alpha-synuclein levels. These effects were inhibited when the cells were treated with a CB1 receptor-selective antagonist, which indicates that the biological effects of cannabidiol are mediated via its interaction with CB1 receptor. Additionally, we also observed that cannabinoid compounds induce autophagy and alpha-synuclein degradation after they interact with the CB1 receptor. In summary, our data suggest that cannabidiol induces autophagy and reduces cytosolic alpha-synuclein levels. These biological effects are mediated preferentially through the interaction of cannabidiol with CB1 receptors, and therefore, cannabinoid compounds that act selectively on this receptor could represent a new approach for autophagy modulation and degradation of protein aggregates. (AU)

• FAPESP's process: 19/02821-8 - Autophagy modulation by cannabinoids: neuroprotection in Parkinson's Disease
• Grantee: Soraya Soubhi Smaili
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 19/14722-4 - Two-Pore Channels receptors and TFEB-3 autophagy modulation in human hepatocellular carcinoma
• Grantee: Gustavo José da Silva Pereira
• Support Opportunities: Regular Research Grants
• FAPESP's process: 13/20073-2 - Autophagy as a protective mechanism in senescent rats
• Grantee: Soraya Soubhi Smaili
• Support Opportunities: Regular Research Grants
• FAPESP's process: 20/08840-1 - Study of autophagy and neuroprotection mediated by cannabinoids compounds in vitro and in vivo models of Parkinson's Disease
• Grantee: Adolfo Garcia Erustes
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 17/10863-7 - Study of lipophagy mediated by two-pore channels receptors
• Grantee: Gustavo José da Silva Pereira
• Support Opportunities: Regular Research Grants