Fig. 6.

The Prion-like propagation of CryAB^R120G protein in cell cultures. a Protein aggregates in primary mixed neuron-glia cultures detected with a Proteostat aggresome detection kit following incubation with the exosomes (Exo) isolated from Ntg or CryAB^R120G mice. Scale bar, 50 μm. b Quantitative analysis of (a). c Cultured neurons treated with CryAB^R120G exosomes showed a reduced ATP level. d Schematic illustration of cell culture assay to determine the prion-like property of CryAB^R120G protein. e Immunocytochemical staining of transfected myc-flag-tagged wild-type mouse CyAB in neural cells following transduction of CryAB^R120G aggregate seeds. Scale bar, 20 μm. f Quantitative analysis of (e). g Hypothetical model explaining the prion-like propagation of misfolded CryAB^R120G protein from the heart to brain. Exosomes containing CryAB^R120G protein can be transported from the heart to brain through blood circulation. In the brain, CryAB^R120G protein propagates in a prion-like phenomenon, and causes increased neuroinflammation and abnormal brain function. Data are shown as mean ± SD; n = 6 for (c) and n = 3 for (b), (f). *p < 0.05, **p < 0.01