title: Autophagy flux induced by ginsenoside-Rg3 attenuates human prion protein-mediated neurotoxicity and mitochondrial dysfunction.
abstract: Mitochondrial quality control is a process by which mitochondria undergo successive rounds of fusion and fission with dynamic exchange of components to segregate functional and damaged elements. Removal of mitochondrion that contains damaged components is accomplished via autophagy. In this study, we investigated whether ginsenoside Rg3, an active ingredient of the herbal medicine ginseng that is used as a tonic and restorative agent, could attenuate prion peptide, PrP (106-126)-induced neurotoxicity and mitochondrial damage. To this end, western blot and GFP-LC3B puncta assay were performed to monitor autophagy flux in neuronal cells; LC3B-II protein level was found to increase after Rg3 treatment. In addition, electron microscopy analysis showed that Rg3 enhanced autophagic vacuoles in neuronal cells. By using autophagy inhibitors wortmannin and 3-methyladenine (3MA) or autophagy protein 5 (Atg5) small interfering RNA (siRNA), we demonstrated that Rg3 could protect neurons against PrP (106-126)-induced cytotoxicity via autophagy flux. We found that Rg3 could also attenuate PrP (106-126)-induced mitochondrial damage via autophagy flux. Taken together, our results suggest that Rg3 is a possible therapeutic agent in neurodegenerative disorders, including prion diseases.
authors.affiliation: Biosafety Research Institute, College of Veterinary Medicine, Chonbuk National University, Iksan, Jeonbuk, South Korea.
authors.forename: Ji-Hong
authors.initials: JH
authors.lastname: Moon
authors.affiliation: Biosafety Research Institute, College of Veterinary Medicine, Chonbuk National University, Iksan, Jeonbuk, South Korea.
authors.forename: Ju-Hee
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Biosafety Research Institute, College of Veterinary Medicine, Chonbuk National University, Iksan, Jeonbuk, South Korea.
authors.forename: You-Jin
authors.initials: YJ
authors.lastname: Lee
authors.affiliation: Biosafety Research Institute, College of Veterinary Medicine, Chonbuk National University, Iksan, Jeonbuk, South Korea.
authors.forename: Sang-Youel
authors.initials: SY
authors.lastname: Park
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy / Q000187:drug effects* / Q000502:physiology; D045744:Cell Line, Tumor; D036145:Ginsenosides / Q000494:pharmacology*; D006801:Humans; D008928:Mitochondria / Q000187:drug effects* / Q000502:physiology; D009474:Neurons / Q000187:drug effects*; D011328:Prions / Q000633:toxicity*; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology
chemical_list: D036145:Ginsenosides; D011328:Prions; C097367:ginsenoside Rg3; C025946:3-methyladenine; D051057:Proto-Oncogene Proteins c-akt; D000225:Adenine
keywords: Gerotarget; autophagy; ginsenoside Rg3; mitochondria; neuron; prion