Genes 2 Brains 2 Mind 2 Me

Mouse models of complex neurological illness are a powerful means to dissect molecular pathways and treatment paradigms. Current mouse models for the tremors and movement difficulties seen in Parkinson disease include genes such as parkin, alpha-synuclein, LRRK2, PINK1 and DJ-1. These models however, do not show the motor control problems and spontaneous degeneration of dopamine neurons as seen in PD in human patients. A new mouse model as reported by Kittappa and colleagues, unlike previous models, does, however, show amazing verisimilitude to PD. In their paper, “The foxa2 Gene Controls the Birth and Spontaneous Degeneration of Dopamine Neurons in Old Age” (DOI) the authors find that mice with only a single copy of the foxa2 gene acquire motor deficits and a late-onset degeneration of dopamine neurons. The age-related spontaneous cell death preferentially affects dopamine producing neurons in the substantia nigra that are affected in PD. The link between genetic risk and environmental exposure to oxidative toxins, a known risk factor in PD, is remarkably straightforward as foxa2 appears to be a regulator of superoxide dismutase, a potent protective scavenger of damage-inducing free radicals. More amazingly still, the authors demonstrate that foxa2 plays a key role in the birth of dopamine neurons – thus opening up new therapeutic possibilities of simultaneously producing new neurons and blocking apoptotic death of old ones. This fox brings new hope for treatment !