SNCA and Parkinson disease: These two sites have also been combined into a dual-hit hypothesis, centered on an external agent simultaneously entering the organism via the two routes.12 Whether with an initially external origin or endogenously generated, the theory that a misfolded, prion-like self-propagating form of alpha-synuclein is responsible for the disease is another major hypothesis currently under investigation.9,13 More endogenous, aging-related perspectives of sporadic PD focus on the role of oxidative stress and mitochondrial damage, for which there is significant evidence in PD patients.