• Authors: Woo TG. et al.
  • Year: 2021
  • Journal: Commun Biol 4 1397
  • Applications: in vitro / DNA / jetOPTIMUS, jetPEI
  • Cell types:
    1. Name: HEK-293
      Description: Human embryonic kidney Fibroblast
      Known as: HEK293, 293
    2. Name: SK-N-MC
      Description: Human neuroblastoma cells
    3. Name: SK-N-SH
      Description: Human bone marrow neuroblastoma


GFP-SOD1 (WT; #26402, G85R; #26405, G93A; #26406), non-tagged SOD1 (WT; #26397, A4V; #26398, G37R; #26399, G85R; #26400, G93A; #26401), tdTomato-TDP43 expression vectors (#28205) were purchased from Addgene (Cambridge, MA, USA). Transfection was performed using Jet-PEI reagent or Jet-Optimus (JetPEI and JetOptimus; Polyplus transfection, New York, NY, USA) according to the manufacturer’s protocol. Briefly, the vector was mixed with JetPEI reagent in 150 mM NaCl buffer or JetOptimus reagent in JetOptimus buffer, then the mixture was incubated for 15 min. The mixture was added to cells in serum-free medium for 4 h. After incubation, cells were replaced with a culture medium supplemented with 10% FBS


Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease characterized by selective death of motor neurons. Mutations in Cu, Zn-superoxide dismutase (SOD1) causing the gain of its toxic property are the major culprit of familial ALS (fALS). The abnormal SOD1 aggregation in the motor neurons has been suggested as the major pathological hallmark of ALS patients. However, the development of pharmacological interventions against SOD1 still needs further investigation. In this study, using ELISA-based chemical screening with wild and mutant SOD1 proteins, we screened a new small molecule, PRG-A01, which could block the misfolding/aggregation of SOD1 or TDP-43. The drug rescued the cell death induced by mutant SOD1 in human neuroblastoma cell line. Administration of PRG-A01 into the ALS model mouse resulted in significant improvement of muscle strength, motor neuron viability and mobility with extended lifespan. These results suggest that SOD1 misfolding/aggregation is a potent therapeutic target for SOD1 related ALS.