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

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), leucinerich
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 alphasynuclein,
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.