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Background  The identification of a DNA variant in  pyridoxal kinase  ( Pdxk ) associated with increased risk to Parkinson disease (PD) gene led us to study the inhibition of this gene in the  Dopa decarboxylase  ( Ddc )-expressing neurons of the well-studied model organism  Drosophila melanogaster . The multitude of biological functions attributable to the vitamers catalysed by this kinase reveal an overabundance of possible links to PD, that include dopamine synthesis, antioxidant activity and mitochondrial function. Drosophila possesses a single homologue of  Pdxk  and we used RNA interference to inhibit the activity of this kinase in the  Ddc - Gal4 -expressing neurons. We further investigated any association between this enhanced disease risk gene with the established PD model induced by expression of  α - synuclein  in the same neurons. We relied on the pro-survival functions of Buffy, an anti-apoptotic  Bcl - 2  homologue, to rescue the Pdxk-induced phenotypes.    Results  To drive the expression of  Pdxk  RNA interference in DA neurons of Drosophila, we used  Ddc - Gal4  which drives expression in both dopaminergic and serotonergic neurons, to result in decreased longevity and compromised climbing ability, phenotypes that are strongly associated with Drosophila models of PD. The inhibition of  Pdxk  in the  α - synuclein -induced Drosophila model of PD did not alter longevity and climbing ability of these flies. It has been previously shown that deficiency in vitamers lead to mitochondrial dysfunction and neuronal decay, therefore, co-expression of  Pdxk - RNAi  with the sole pro-survival  Bcl - 2  homologue  Buffy  in the  Ddc - Gal4 -expressing neurons, resulted in increased survival and a restored climbing ability. In a similar manner, when we inhibited  Pdxk  in the developing eye using  GMR - Gal4 , we found that there was a decrease in the number of ommatidia and the disruption of the ommatidial array was more pronounced. When  Pdxk  was inhibited with the  α - synuclein -induced developmental eye defects, the eye phenotypes were unaltered. Interestingly co-expression with  Buffy  restored ommatidia number and decreased the severity of disruption of the ommatidial array.    Conclusions  Though  Pdxk  is not a confirmed Parkinson disease gene, the inhibition of this kinase recapitulated the PD-like symptoms of decreased lifespan and loss of locomotor function, possibly producing a new model of PD.

A loss of Pdxk model of Parkinson disease in Drosophila can be suppressed by Buffy