Parkinson's disease (PD) is caused by a progressive deterioration of the neurons that control movement and contain dopamine, but the mechanism by which dopaminergic neurons are selectively lost has been unclear. In June Nature Medicine Jin Xu and colleagues from Harvard Medical School show that the widely abundant brain protein α-synuclein may be responsible for the nerve destruction in PD (Nat Med 2002, 8:600-606).

Xu et al. used a model of a-synuclein accumulation in cultures of human fetal dopaminergic neurons and non-dopaminergic human cortical neurons. They observed that accumulation of α-synuclein in dopaminergic neurons results in apoptosis that requires endogenous dopamine production and is mediated by reactive oxygen species. In contrast, α-synuclein is not toxic in non-dopaminergic neurons, but conversely exhibits neuroprotective activity.

In addition, they found that soluble protein complexes that contain α-synuclein and 14-3-3 protein chaperones, mediate dopamine-dependent neurotoxicity in PD.

"Xu et al. provide...