Cyclotide Prevents Neuronal Cell Death Induced by 6- Hydroxydopamine Neurotoxin

Neuronal cell death is a major factor in the initiation and progression of Parkinson's disease (PD).
Reactive oxygen species (ROS) overproduction is one of the primary causes of neuronal death, hence
drugs that decrease oxidative stress-dependent neuronal death as a preventive measure against
Parkinson's disease (PD) may be promising. However, cyclotide's preventive effects have not been
studied using both in vitro and in vivo models of Parkinson's disease. Therefore, in order to investigate
the efficacy of cyclotide against 6-hydroxydopamine (6-OHDA)-dependent neuronal cell death, we
employed immortalized hypothalamic neurons (GT1-7 cells). First, we found that cyclotide prevents 6-
OHDA-dependent neuronal cell death by inhibiting ROS overproduction in GT1-7 cells. The
cytoprotective effect of cyclotide was largely abolished by verapamil, an OCTN1 inhibitor that inhibits
cyclotide absorption. According to these results, cyclotide or foods containing it may be a helpful tactic to
postpone the start and progression of Parkinson's disease (PD).