What is it about?
For decades, Parkinson's Disease has been considered a state of dopamine deficiency in the basal ganglia. Accordingly, dopaminergic therapies became the standard of care. Yet no study reported the levels of dopamine in the dopaminergic neuron's cytoplasm, the site of dopamine-mediated toxicity. This is the first report of cytosolic dopamine levels in Parkinson's patients's dopaminergic neurons relative to the levels in people without Parkinson's. The neurons in the caudate had cytoplasmic dopamine levels over 80% higher than normal and in the putamen were 460% of normal. This cytoplasmic dopamine excess explains why dopaminergic therapy does not change the progression of the disease and establishes a new target for treatment.
Why is it important?
With standard treatments meaningfully unchanged since the 1970s, Parkinson's patients need reevaluation of the disease pathophysiology assumptions and exploration of how new therapeutic targets can be identified. This manuscript does both.