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- Parkinson's disease: substrate proteins and E2 enzymes involved in Parkin pathwayPublication . Guerreiro, Patrícia I. da Silva; Johnston, Jennifer A.Parkinson’s disease (PD) is one of the most common age-related neurodegenerative disorders, resulting from the degeneration and death of dopaminergic neurons and the consequent loss of a neurotransmitter dopamine. The molecular genetics of this process remains unclear but studies from PD inherited forms identified a mutated Parkin gene as responsible for almost 50% of autosomal-recessive juvenile parkinsonism (AR-JP). To better understand parkin’s role in PD the present study focused on several cellular assays using HEK-293 cells, mice brain samples and human cortical cells, evaluating the interaction of parkin protein with p38 and Eps15, two potential protein substrates, and five E2 enzymes UbcH2, UbcH5, UbcH6, UbcH7 and UbcH10. The interaction of p38 and Eps15 protein with parkin was demonstrated in some particularly assays. The results highlight the importance of tagged parkin, with Flag or GST epitopes, to analyze specific interaction between p38 and Eps15 proteins. UbcH2, UbcH7 and UbcH10 E2 enzymes interact with parkin protein and open new hypothesis for parkin’s function in several cellular processes. Initially based on some published results, this study reveals new important lines in the research of parkin protein pathway.