Mutant SOD1-mediated HuWtSOD1 misfolding is transmissible between cells. (A) IP of lysates from naïve HEK cells cultured in the presence of conditioned medium from one, three, and five passages of transduction assays initiated by different SOD1 variants. mIgG2a, mouse IgG2a isotype control; rIgG, rabbit mixed IgG control; SOD1, pan-SOD1 antibody; 3H1 and 10C12, misfolded SOD1-specific antibodies. (B) SOD1 knockdown abolishes detectable misfolding. IP of lysates from HEK cells with knocked down SOD1 expression cultured in the presence of conditioned medium from HEK cells transfected with empty vector control (EV), SOD1-G85R, SOD1-G127X, or HuWtSOD1. (C) IP of lysates from naïve primary neural cell cultures derived from embryonic spinal cord of HuWtSOD1 transgenic or nontransgenic littermate (n-Tg) mice incubated in the presence of conditioned from SOD1-G127X or empty vector (EV)-transfected HEK293 cells.