HQ-415 is active in the TDP-43 model, but CQ was not HQ-161 and HQ-415 is retested in the dose for their ability to rescue TDP-43. HQ-415 strongly synergizes with CQ at multiple concentrations in cells expressing α-syn. CQ fails to synergize with HQ-161 and actually antagonizes HQ-161 rescuing activity, in TDP-43-expressing cells. In contrast, despite the fact that CQ was completely inactive against TDP-43, it strongly synergized with HQ-415, decreasing the EC50 from 16 to 5 μM. Both HQ-161 and HQ-415 rescue TDP-43 toxicity. In cells expressing α-syn, HQ-161, despite being inactive on its own, synergized with HQ-415, reducing the EC50 from 21 to 14 μM.