Prion diseases are fatal brain disorders induced by PrPSc, a misfolded, aggregation-prone isoform of the host’s prion protein. Despite extensive research, the specific molecular mechanisms underlying neuronal death in prion diseases remain poorly understood. However, the accumulation of PrPSc in brain tissue can activate inflammatory responses via the release of pro-inflammatory cytokines and reactive oxygen species (ROS) [1], which subsequently contribute to neuronal damage and death. Furthermore, cellular stress responses identified in the brains of patients with Creutzfeldt-Jakob disease (CJD) [2] highlight the role of oxidative stress in the pathophysiology of CJD. As a result, minimizing oxidative stress is likely to be a reasonable strategy for delaying the development of prion diseases. Mesenchymal stem cells (MSCs) have been widely studied as potential therapy in several prion disease models [3]. However, mechanism by which MSCs exert their effects on prion disease is still poorly understood. It has been reported that the secretome released by stem cells contains substances such as microvesicles, exosomes, proteins, and cytokines and promotes tissue repair and regeneration [4]. The prion protein peptide (PrP106–126) has various physicochemical and biological characteristics in common with PrPSc, including the induction of oxidative stress, making it commonly used for replicating prion disease changes in vitro [5]. Based on our previous study, we optimized conditions using various concentrations of PrP106–126 peptide (KTNMKHMAGAAAAGAVVGGLG) (synthesized by Peptron, Yuseong-gu) and found that treatment with 100 µM PrP106–126 for 24 h significantly induced neurotoxicity [6]. Herein, we aimed to explore the potential protective effects of the secretome released from adipose-derived MSCs (AdMSC secretome) against PrP106–126-induced oxidative stress and to elucidate the underlying mechanisms in the SH-SY5Y cell line, a commonly used in vitro model for prion disease.
