In discerning that established components of the systemic gene silencing machinery of C. elegans, SID-1 and SID-3, can function as effectors of α-syn-induced DA neurodegeneration, we provide a roadmap for future investigation of conserved targets of their activity in modulating neurodegenerative disease, including numerous previously unrecognized neuroprotective gene products. The gene discussed is SIDT1; the disease is neurodegenerative disease.