Cannabidiol exerts protective effects in an in vitro model of Parkinson’s disease activating AKT/mTOR pathway.

Publication date: Mar 14, 2020

Parkinson’s disease (PD) is a neurodegenerative disorder characterized by the degeneration of the nigrostriatal dopaminergic pathway with loss of substantia nigra pars compacta neurons and dopamine depletion. Various natural compounds showed protective actions against PD. In this work, the protective effects of cannabidiol (CBD), obtained from Cannabis sativa, were evaluated in retinoic acid differentiated SH-SY5Y cells exposed to 1-methyl-4-phenylpyridinium (MPP), an in vitro PD model. In order to evaluate which receptor is involved in CBD actions CB1, CB2 and TRPV1 receptor antagonists were used. CBD counteracted the loss of cell viability caused by MPP, reducing apoptosis as demonstrated by the reduction of Bax and caspase 3. Moreover, CBD reduced the nuclear levels of PARP-1. The protective effects of CBD seem to be mediated by the activation of ERK and AKT/mTOR pathways. The treatment with AKT1/2 inhibitor and the mTOR inhibitor rapamycin abolished CBD protective effects. The CBD-induced ERK activation may be mediated by CBD interaction with CB2 and TRPV1. We also investigated the protein levels of the autophagic proteins LC3 and beclin 1. CBD reduced the MPP-induced increase of LC3 by CB2 and TRPV1 receptors. These data suggested the involvement of ERK in the modulation of autophagy. However, beclin 1 levels were not modified neither by MPP nor by CBD. These results indicated that CBD may exert preventive and protective actions in PD.

Gugliandolo, A., Pollastro, F., Bramanti, P., and Mazzon, E. Cannabidiol exerts protective effects in an in vitro model of Parkinson’s disease activating AKT/mTOR pathway. 24395. 2020 Fitoterapia.

Concepts Keywords
AKT PD neurodegenerative disorder
AKT1 Branches of biology
Apoptosis Medicine
Autophagic Signal transduction
Autophagy Ion channels
Bax Oncology
Cannabidiol MTOR
Cannabis Sativa TRPV1
Caspase Cannabinoids
CB1 Resorcinols
CB2 Protein kinase B
CBD Cannabidiol
Dopamine Apoptosis
Dopaminergic Pathway
Neurodegenerative Disorder
Retinoic Acid


Type Source Name
drug DRUGBANK Cannabidiol
disease MESH neurodegenerative disorder
drug DRUGBANK Dopamine
drug DRUGBANK Tretinoin
pathway KEGG Apoptosis
drug DRUGBANK Sirolimus
pathway KEGG Autophagy


Original Article

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