Transcriptome Highlights Cannabinol Modulation of Mitophagy in a Parkinson's Disease In Vitro Model

Parkinson's disease (PD) is a neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra and the accumulation of α-synuclein aggregates, known as Lewy bodies. It is known that mitochondria dysfunctions, including impaired localization, transport and mitophagy, represent features of PD. Cannabinoids are arising as new therapeutic strategies against neurodegenerative diseases. In this study, we aimed to evaluate the potential protective effects of cannabinol (CBN) pre-treatment in an in vitro PD model, namely retinoic acid-differentiated SH-SY5Y neuroblastoma cells treated with 1-methyl-4-phenylpyridinium (MPP⁺). With this aim, we performed a transcriptomic analysis through next-generation sequencing. We found that CBN counteracted the loss of cell viability caused by MPP⁺ treatment. Then, we focused on biological processes relative to mitochondria functions and found that CBN pre-treatment was able to attenuate the MPP⁺-induced changes in the expression of genes involved in mitochondria transport, localization and protein targeting. Notably, MPP⁺ treatment increased the expression of the genes involved in PINK1/Parkin mitophagy, while CBN pre-treatment reduced their expression. The results suggested that CBN can exert a protection against MPP⁺ induced mitochondria impairment.