A Common NURR1 Polymorphism Associated With Parkinson Disease and Diffuse Lewy Body Disease

Abstract
EVIDENCE IS accumulating that genetic factors play an important role in determining the risk of developing Parkinson disease (PD).1 The identification of specific genes that influence PD risk may reveal clues regarding PD pathogenesis and potential neuroprotective therapies. One such candidate gene is NURR1, a transcription factor that is highly expressed in dopaminergic neurons in the substantia nigra.2,3Nurr1-deficient mice lack mesencephalic dopaminergic neurons.4,5 Heterozygote Nurr1-deficient mice, with only 1 functional copy of the Nurr1 gene, develop normal tyrosine hydroxylase–positive neurons in the substantia nigra, but show enhanced susceptibility to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) toxicity.6