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Cannabidiol exerts protective effects in an in vitro model of Parkinson's disease activating AKT/mTOR pathway.
Fitoterapia. 2020 Jun; 143:104553.F

Abstract

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.

Authors+Show Affiliations

IRCCS Centro Neurolesi "Bonino Pulejo", Via Provinciale Palermo, Contrada Casazza, 98124 Messina, Italy.Dipartimento di Scienze del Farmaco, Università del Piemonte Orientale, Largo Donegani 2, 28100 Novara, Italy.IRCCS Centro Neurolesi "Bonino Pulejo", Via Provinciale Palermo, Contrada Casazza, 98124 Messina, Italy.IRCCS Centro Neurolesi "Bonino Pulejo", Via Provinciale Palermo, Contrada Casazza, 98124 Messina, Italy. Electronic address: emanuela.mazzon@irccsme.it.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32184097

Citation

Gugliandolo, Agnese, et al. "Cannabidiol Exerts Protective Effects in an in Vitro Model of Parkinson's Disease Activating AKT/mTOR Pathway." Fitoterapia, vol. 143, 2020, p. 104553.
Gugliandolo A, Pollastro F, Bramanti P, et al. Cannabidiol exerts protective effects in an in vitro model of Parkinson's disease activating AKT/mTOR pathway. Fitoterapia. 2020;143:104553.
Gugliandolo, A., Pollastro, F., Bramanti, P., & Mazzon, E. (2020). Cannabidiol exerts protective effects in an in vitro model of Parkinson's disease activating AKT/mTOR pathway. Fitoterapia, 143, 104553. https://doi.org/10.1016/j.fitote.2020.104553
Gugliandolo A, et al. Cannabidiol Exerts Protective Effects in an in Vitro Model of Parkinson's Disease Activating AKT/mTOR Pathway. Fitoterapia. 2020;143:104553. PubMed PMID: 32184097.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cannabidiol exerts protective effects in an in vitro model of Parkinson's disease activating AKT/mTOR pathway. AU - Gugliandolo,Agnese, AU - Pollastro,Federica, AU - Bramanti,Placido, AU - Mazzon,Emanuela, Y1 - 2020/03/14/ PY - 2020/01/09/received PY - 2020/03/10/revised PY - 2020/03/11/accepted PY - 2020/3/19/pubmed PY - 2021/1/28/medline PY - 2020/3/19/entrez KW - AKT KW - Cannabidiol KW - Differentiated SH-SY5Y KW - ERK KW - In vitro Parkinson's disease KW - mTOR SP - 104553 EP - 104553 JF - Fitoterapia JO - Fitoterapia VL - 143 N2 - 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. SN - 1873-6971 UR - https://www.unboundmedicine.com/medline/citation/32184097/Cannabidiol_exerts_protective_effects_in_an_in_vitro_model_of_Parkinson's_disease_activating_AKT/mTOR_pathway_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0367-326X(20)30135-0 DB - PRIME DP - Unbound Medicine ER -