Diseases that occur in familial and sporadic forms present serious challenges to researchers, but lend themselves to the discovery of common biological pathways. This situation is exemplified by recent work on a fly model of Parkinson disease (PD), which has revealed a genetic link between the familial and sporadic forms of the disease.

The authors were drawn to a particular gene, DJ1, by its involvement in the familial form of PD, and went on to identify two close gene homologues in Drosophila melanogaster (DJ1α and DJ1β). Flys in which one or both of these genes were knocked out were viable and fertile; however, those that were exposed to toxins that influence sporadic PD — such as the herbicide paraquat and the insecticide rotenone — were strikingly more sensitive than normal animals. It's as though a lack of DJ1 — in particular DJ1β — renders organisms more susceptible to environmental toxins, leading ultimately to more rapid death, just as in sporadic PD in humans. DJ1β also shifts to a more acidic form on exposure to these toxins; this isoform might therefore directly influence DJ1 activity, setting up further research that could shed light into mechanisms of DJ1 anti-oxidant function.

This work reinforces the usefulness of animal models for studying gene and environment interactions in human disease and proposes DJ1 as an attractive drug target, given that the same pathway is probably involved in both forms of PD. It also sets out goals for more research into this biological pathway — including resolving potential interactions between the two DJ1 isoforms in protection from toxins, as described in an accompanying paper by Menzies and colleagues.