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-synuclein, which is a key part of Lewy bodies, in PARK one in 1997 and parkin in PARK 2 in 1998, that's an E3 ubiquitin ligase and causes endoplasmic reticulum (ER) strain, advise that dysfunction of the intracellular proteinase devices, including ubiquitin-proteasome process or lysosomal program, which eliminates pointless toxic proteins in cells