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.
Highlights
Prion diseases or transmissible spongiform encephalopathies (TSEs) are inevitably lethal neurodegenerative conditions that can influence humans and various kinds of animals [1]
We investigated the influence of Rg3 on PrP (106-126)-induced neurotoxicity in primary neuronal cells and a neuroblastoma cell line by using annexin V assay
This study showed that Rg3 could attenuate prion protein-induced neurotoxicity and mitochondrial dysfunction via autophagy flux
Summary
Prion diseases or transmissible spongiform encephalopathies (TSEs) are inevitably lethal neurodegenerative conditions that can influence humans and various kinds of animals [1]. They may present with certain morphological and pathophysiological features that parallel those of other progressive encephalopathies, including Alzheimer’s disease and Parkinson’s disease [2]. It was later shown that PrPC, a cellular prion protein, may undergo disease-associated and diagnostically important modifications without becoming protease-resistant (protease-sensitive PrPSc, or sPrPSc) [3]. The biological activity of the 106-126 sequence has been further proved by the observation that this fragment has AGAAAAGA sequence (amino acids 113 to 120) shown to have specific region within PrP molecules in many kinds of species [9]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
