Lessons from Drosophila models of DJ-1 deficiency.

Mutations in the DJ-1 gene are associated with rare forms of autosomal recessive early-onset Parkinson's disease (PD). Although the precise physiological function of DJ-1 remains obscure, accumulating evidence suggests that DJ-1 may normally function as a redox-sensitive molecular chaperone that can protect against the deleterious effects of oxidative stress, particularly in mitochondria. Recent studies in the fruit fly, Drosophila melanogaster, have shed further light on the biological role of DJ-1. DJ-1-deficient Drosophila models exhibit distinct phenotypes but collectively highlight a prominent neuroprotective role for DJ-1 against oxidative insult. However, Drosophila lacking DJ-1 do not consistently produce a useful PD-like phenotype (that is, they generally fail to exhibit degeneration of neurons that contain the neurotransmitter dopamine), which may reflect putative compensatory neuroprotective mechanisms. DJ-1-deficient fly models further highlight the utility of Drosophila as an important tool for elucidating protein function and for modeling neurodegenerative disease.