Rutin Alleviates Prion Peptide-Induced Cell Death Through Inhibiting Apoptotic Pathway Activation in Dopaminergic Neuronal Cells

Prion disorders are progressive neurodegenerative diseases characterized by extensive neuronal loss and accumulation of the abnormal form of the scrapie prion protein (PrP). Rutin is a flavonoid that occurs naturally in plant-derived beverages and foods and is used in traditional and folkloric medicine worldwide. In the present study, we evaluated the protective effects of rutin against PrP fragment (106-126)-induced neuronal cell death. Rutin treatment blocked PrP(106-126)-mediated increases in reactive oxygen species production and nitric oxide release and helped slowing the decrease of neurotrophic factors that results from PrP accumulation. Rutin attenuated PrP(106-126)-associated mitochondrial apoptotic events by inhibiting mitochondrial permeability transition and caspase-3 activity and blocking expression of the apoptotic signals Bax and PARP. Additionally, rutin treatment significantly decreased the expression of the death receptor Fas and its ligand Fas-L. Overall, our results demonstrated that rutin protects against the neurodegenerative effects of prion accumulation by increasing production of neurotropic factors and inhibiting apoptotic pathway activation in neuronal cells. These results suggested that rutin may have clinical benefits for prion diseases and other neurodegenerative disorders.