Project description:We investigated the gene expression profiles of U373MG human astrocytoma cells treated with vehicle (DMSO) or edaravone or carnosic acid) or both edaravone and carnosic acid. Edaravone is a free radical scavenger sold as radicut. Carnosic acid is a phytochemical found in rosemary and sage.
Project description:Researchers have induced an experimental model of multiple sclerosis [experimental autoimmune encephalomyelitis (EAE)] in C57BL/6 mice to test the neuro-therapeutic effect of Compound Edaravone (CEDA, Jiangsu Simcere Pharmaceutical Co., Ltd., Nanjing, China) during the disease peak and investigate its possible mechanisms
Project description:Edaravone is a free-radical scavenger drug that was recently approved for the treatment of amyo-trophic lateral sclerosis (ALS), a neurodegenerative disease. A pathological hallmark of ALS is the accumulation of ubiquitinated or phosphorylated aggregates of the 43-kDa transactive response DNA binding protein (TDP-43) within the cytoplasm of motor neurons. This study revealed the efficacy of edaravone in preventing neuronal cell death in a TDP-43 proteinopathy model and analyzed the molecular changes associated with the neuroprotection. The viability of the neuronal cells expressing TDP-43 was reduced by oxidative stress, and edaravone (≥10 μmol/L) protected in a concentration-dependent manner against the neurotoxic insult. Differential gene expression analysis revealed changes among pathways related to nuclear erythroid 2-related-factor (Nrf2)-mediated oxidative stress response in cells expressing TDP-43. In edaravone-treated cells express-ing TDP-43, significant changes in gene expression were also identified among Nrf2-oxidative re-sponse, unfolded protein response, and autophagy pathways. In addition, the expression of genes belonging to phosphatidylinositol metabolism pathways was modified. These findings suggest that the neuroprotective effect of edaravone involves the prevention of TDP-43 misfolding and en-hanced clearance of pathological TDP-43 in TDP-43 proteinopathy.
Project description:Brain tumour stem cells (BTSCs) are a population of self-renewing malignant stem cells that play an important role in glioblastoma tumour hierarchy and contribute to tumour growth, therapeutic resistance, and tumour relapse. Thus, targeting of BTSCs within the bulk of tumours represents a crucial therapeutic strategy. Here, we report that Edaravone is a potent drug that impairs BTSCs and impedes glioblastoma tumorigenesis. We show that Edaravone inhibits the self-renewal and growth of BTSCs harbouring a diverse range of oncogenic mutations without affecting non-oncogenic neural stem cells. Global gene expression profiling revealed that Edaravone significantly alters BTSC transcriptome and attenuates the expression of a large panel of genes involved in cell cycle progression, stemness, and DNA repair mechanisms. Mechanistically, we discovered that Edaravone directly targets Notchless homolog 1 (NLE1) and impairs Notch signalling pathway, alters the expression of stem cell markers, and sensitizes BTSC response to ionizing radiation (IR)-induced cell death. Importantly, we show that Edaravone treatment in preclinical models delays glioblastoma tumourigenesis, sensitizes their response to IR and prolongs the lifespan of animals. Our data suggest that repurposing of Edaravone is a promising therapeutic strategy for glioblastoma patients.
