α-synuclein overexpression induces apotosis in dopaminergic neurons (red).
Xu/Macmillan
Aggregations of α-synuclein are a hallmark of Parkinson's disease (PD), and mutations in its gene are associated with familial forms of the disease. Yankner wanted to know why the protein is so toxic. When he overexpressed either wild-type or mutant forms of α-synuclein in cultured human dopaminergic neurons (DAN cells)—the cells affected in PD—a large number of the cells underwent apoptosis. In contrast, excess α-synuclein seemed to protect the nondopaminergic cortical neurons from apoptosis.
If endogenous synthesis of dopamine was blocked by the addition of a tyrosine hydroxylase inhibitor (THI), overexpression of α-synuclein no longer induced apoptosis. Thus, somehow, it is the combination of α-synuclein and dopamine that causes cell death, rather than overexpression of α-synuclein...
