Flow chat of the linkage between PD and melanoma mediated by α-Syn.

<p>In skin melanocytes, UVR causes DNA damage, leading to the initiation of melanoma. UVR also induces melanin synthesis which is catalyzed by TYR. Increased melanin prevents UVR-induced DNA damage, reducing the vulnerability to development of melanoma. α-Syn expression in skin melanocytes may interact with TYR, inhibiting UVR-induced TYR activation, leading to the reduction of melanin synthesis, which may enhance the susceptibility of skin melanocytes to develop melanoma. In brain dopaminergic neurons, impaired degradation of α-Syn or α-Syn multiplications causes accumulation/aggregation of α-Syn, leading to the loss of α-Syn function, thereafter, the decrease of DA release and increase of cellular DA content, which may be converted into melanin in lysosome. The increased melanin content in dopaminergic neurons (neuromelanin) enhances the susceptibility to oxidative stress-induced neuronal injury relevant to PD.