FIGURE 5.

Mutant SOD1 is transferred to spinal neurons through astrocyte-derived exosomes. Electron microscopy pictures of exosomes with characteristic cup-shaped morphology from non-transgenic (ntg) (A) and G93A SOD1-expressing (B) astrocytes (scale bar, 100 nm). Immunoelectron microscopy using anti-human SOD1 antibody indicated SOD1 exclusively inside exosomes isolated from transgenic human SOD1-overexpressing astrocytes (in this case G93A SOD1; see also supplemental Fig. S1A for WT SOD1). C and D, two representative images at different magnification (scale bar, 500 nm) of cultured non-transgenic spinal neurons exposed to G93A SOD1-containing exosome-depleted fractions, showing the 10-nm electron-dense round gold particles labeling human SOD1 only outside the cell; treatment with G93A SOD1-containing exosomes (E and F) caused the diffusion inside the cytoplasm of the majority of human SOD1 (scale bar, 500 nm). The same results were obtained with WT SOD1-containing exosomes (supplemental Fig. S1B). The arrows indicate the plasma membrane of a motor neuron (MN).