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

Autor(es)

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

• Tipo de documento: Artigo Científico
• Fonte: Brain Research; v. 1850, p. 10-pg., 2024-12-24.

Resumo

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)

• Processo FAPESP: 19/02821-8 - Modulação da autofagia por canabinóides: neuroproteção na Doença de Parkinson
• Beneficiário: Soraya Soubhi Smaili
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 19/14722-4 - Receptores two-pore Channels e modulação da autofagia via TFEB-3 no hepatocarcinoma celular humano
• Beneficiário: Gustavo José da Silva Pereira
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 13/20073-2 - Estudo da autofagia no processo de proteção celular de ratas senescentes
• Beneficiário: Soraya Soubhi Smaili
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 20/08840-1 - Estudo da autofagia e neuroproteção mediadas por compostos canabinóides em modelos in vitro e in vivo da Doença de Parkinson
• Beneficiário: Adolfo Garcia Erustes
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 17/10863-7 - Estudo da lipofagia mediada pelos receptores two-pore channels
• Beneficiário: Gustavo José da Silva Pereira
• Modalidade de apoio: Auxílio à Pesquisa - Regular