The presence of protein inclusions in Lewy bodies in PD patients led to the hypothesize that mutations in PARKIN cause a disruption in the E3 ubiquitin ligase activity of PARKIN, leading to insufficient clearance of damaged or mutated substrates and subsequent toxic cellular aggregation of unwanted proteins and neuronal cell death (Shimura et al. 2000). This evidence concerns the gene PRKN and Parkinson disease.