Indeed, our findings are compatible with the ‘dual-hit’ hypothesis of neurodegenerative diseases, as exposure of the SKP1A-knocked down cells to external insults implicated in SN DAergic neuropathology, such as decreased support of neurotrophins or MPP+ (gene–environment interaction), exacerbated the induced damage compared to scrambled vector infected cells. The gene discussed is BDNF; the disease is neurodegenerative disease.