The Convergence of Dopamine and α-Synuclein: Implications for Parkinson’s Disease:

In Parkinson’s disease (PD), the loss of dopamine-producing neurons in the substantia nigra (SN) leads to severe motor impairment, and pathological inclusions known as Lewy bodies contain aggregated α-synuclein protein. The relationship of α-synuclein aggregation and dopaminergic degeneration is unclear. This commentary highlights a recent study showing that the interaction of α-synuclein with dopamine may be an important mechanism underlying disease. Elevating dopamine levels in mice expressing human α-synuclein with the A53T familial PD mutation recapitulated key features of PD, including progressive neurodegeneration of the SN and decreased ambulation. The toxicity of dopamine was dependent on α-synuclein expression; hence, raising dopamine levels in nontransgenic mice did not result in neuronal injury. This interaction is likely mediated through soluble α-synuclein oligomers, which had modified conformations and were more abundant as a result of dopamine elevation in the mouse brain. Specific mutation...