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Wang C, Ko HS, Thomas B, Tsang F, Chew KC, Tay SP, Ho MW, Lim TM, Soong TW, Pletnikova O, Troncoso J, Dawson VL, Dawson TM, Lim KL: Stress-induced alterations in parkin solubility promote parkin aggregation and compromise parkin's protective function. Hum Mol Genet. 2005 Dec 15;14(24):3885-97. Epub 2005 Nov 8.
Mechanistically, our results provide a link between the influence of environmental and intrinsic factors and genetic susceptibilities in PD pathogenesis.
Using both cell culture and in vivo models, we demonstrate here that several PD-linked stressors, including neurotoxins (MPP+, rotenone, 6-hydroxydopamine), paraquat, NO, dopamine and iron, induce alterations in parkin solubility and result in its intracellular aggregation. |
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