A Parkinson disease gene discovered, an oncogene remembered: DJ-1 spurs a rethink on neurodegenerative mechanisms.(Hot Papers)

The discovery of several genes linked to Parkinson disease (PD) in recent years has spawned extensive research efforts to elucidate the underlying mechanism of this prevalent neurological disorder. This issue's Hot Paper focuses on the discovery of a third gene, DJ-1, which is mutated in a small subset of patients with PD. (1) Neurologist and geneticist Vincenzo Bonifati, along with molecular biologists Ben Oostra and Peter Heutink and colleagues at Erasmus University Medical Center in Rotterdam, showed that DJ-1 mutations are implicated in a form of autosomal recessive, early-onset PD. Genetic mapping of regions implicated in parkinsonism among members of two different families revealed a deletion in the DJ-1 gene among members of one family, and a point mutation in members of the other.

Interestingly, the gene had been discovered in a wholly different context several years earlier by Hiroyashi Ariga and colleagues at Hokkaido University in Sapporo. (2) A sleeper of sorts, the paper was rarely cited, but subsequent interest in this earlier discovery exploded following the work from Bonifati's group, spawning a flurry of citations and subsequent papers in the past two years.

The work highlights the third gene known to be linked to familial Parkinsonism and has heightened interest in the function of the DJ-1 protein. Perhaps more significantly, the link renewed debate over mechanistic theories of Parkinsonism and revived interest in the role of oxidative stress to explain the disease mechanism, a theory that had …