Lactoferrin protects against prion protein-induced cell death in neuronal cells by preventing mitochondrial dysfunction

Abstract

Prion disorder-related neurodegenerative diseases are characterized by the accumulation of prion protein (PrP) scrapie isoform (PrPsc) within the central nervous system. PrPsc induces neuronal cell death by increasing intracellular generation of reactive oxygen species (ROS). Lactoferrin (LF) is an 80 kDa protein, which has antioxidant abilities due to the scavenging of ROS. The effects of LF treatment on PrP (106-126)-mediated neurotoxicity and ROS generation were the focus of this study. LF treatment protected against PrP (106-126)-induced neuronal cell death and decreased ROS generation. The reduced ROS generation prevented PrP (106-126)-induced mitochondrial dysfunction. Moreover, PrP (106-126)-induced protein activation including c-Jun N-terminal kinase and caspase-3 were blocked by LF treatment. These results demonstrated that LF protects neuronal cells against PrP (106-126)-mediated neurotoxicity through the scavenging of ROS and provide evidence that LF treatment prevents neuronal cell death caused by PrP (106-126).

Up-Regulation of mRNA Ventricular PRNP Prion Protein Gene Expression in Air Pollution Highly Exposed Young Urbanites: Endoplasmic Reticulum Stress, Glucose Regulated Protein 78, and Nanosized Particles

“…The critical relevance of the protective role of PrP C has been discussed in the context of acute stroke and the pathogenesis of prion diseases [45–51]. Conversion of PrP C to the pathogenic isoform PrP Sc increases the vulnerability to oxidative insults and is a key downstream mediator of cellular stress-induced neuronal apoptosis [46,49,51]. Up-regulation of PrP C protects against environmental neurotoxic metals-induced oxidative stress and apoptotic cell death [48].…”

“…Additional characterization of the myocardial protein PrP C and GRP78/BiP quantification and the full characterization of the particle-like material observed in myocardial fibers, blood vessels and red blood cells by energy filtered TEM [77] would have benefited these studies. This is important because combustion associated metals [10,38,49,51,65] are likely present in the ultrafine PM and could be responsible for the significant ER stress.…”

Lactoferrin, a Pleiotropic Protein in Health and Disease

“…In addition to ROS quenching and DNA protection, there is an additional Lf mechanism of action that was revealed while investigating oxidative burst of neutrophils (159). Indeed, the antioxidant capability of Lf may counteract oxidative burst of neutrophils, which contributes to the pathogenesis of the septic shock (115,219,234).…”

Parkinson's disease and lactoferrin: Analysis of dependent protein networks

“…The motor symptoms of PD result from the death of dopamine generating cells in the substantia nigra, a region of the mid brain (Rakshit et al, 2014). It has proven, some proteins are affected on the PD as iron binding capability (Berlutti et al, 2011) and direct function as cell protector against toxic stresses and regulator of antioxidant transcriptional (Park et al, 2013). Furthermore, it has been reported that iron has a role in onset of Parkinson's disease (PD) when the concentration rises in substantia nigra.…”

“…In spite mutations on aforementioned genes associated with either autosomal dominant or recessive may be affected on PD, we concentrated on associated proteins to LTF the based on construction of protein interaction networks(PIN) according to LTF characteristics in iron binding capability (Berlutti et al, 2011) and direct function as cell protector against toxic stresses (Park et al, 2013). Due to the A C C E P T E D M A N U S C R I P T…”