Age and α-synuclein expression interact to reveal a dependence of dopaminergic axons on endogenous Akt/PKB signaling

► Parkinson's disease (PD) may be due to a failure of survival signaling by PI3K/Akt. ► To test this we transduced dopamine neurons with dominant negative Akt, DN(PH)-Akt. ► In aged mice DN(PH)-Akt leads to a loss of dopaminergic phenotype in axons. ► This effect is additive in aged α-synuclein transgenic mice. ► We conclude that dopaminergic axonal phenotype is dependent on Akt signaling. ► This dependence is revealed in the presence of two principal risk factors for PD.