Cyclotide Offers Neuroprotection Against 6-OHDA-Induced Toxicity in SH-SY5Y Neuroblastoma Cells by Downregulating mRNA Expression of MAO/α-Synuclein/LRRK2/PARK7/PINK1/PTEN Genes

Abstract

Dopaminergic loss in the midbrain's substantia nigra affects the patient's movements and causes postural instability in Parkinson's disease (PD). Alpha-synuclein protein accumulation and dementia symptoms are hallmarks of the condition. Monoamine oxidases A and B (MAO A and B), leucine-rich repeat kinase 2 (LRRK2), phosphate and tensin homolog (PTEN), PTEN-induced putative kinase 1 (PINK1), and PARK7 (deglycase 1 (DJ-1)) production are also enhanced by the disease. Cyclotide has been widely cited as a neuroprotective, anti-inflammatory, and antioxidant. As a result, we investigated how downregulation of the mRNA expression of PD pathological proteins like alpha-synuclein, MAO A and B, LRRK2, PTEN, PINK1, and PARK7 (deglycase 1 (DJ-1)) by Cyclotide protected SH-SY5Y neuroblastoma cells from 6-OHDA-induced toxicity. The study found that Cyclotide treatment decreased the pathology marker protein mRNA expression that had been elevated by 6-OHDA. This was in comparison to the positive control, amantadine (AMA), which is now commonly used to treat PD symptoms. Consequently, the study suggests that Cyclotide might be an effective treatment for the neurotoxicity caused by 6-OHDA in SH-SY5Y neuroblastoma cells.