Prion-like C-Terminal Domain of TDP-43 and α-Synuclein Interact Synergistically to Generate Neurotoxic Hybrid Fibrils

•α-Synuclein and prion-like domain of TDP-43 monomers synergistically promote hybrid fibrils.•Monomers and aggregates of α-Synuclein seed TDP-43 monomers.•TDP-43 fibrils fail to seed α-Synuclein monomers.•Cross-seeded hybrid aggregates are more cytotoxic than homotypic fibrils.