Stress and Degeneration

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Science  28 May 2004:
Vol. 304, Issue 5675, pp. 1207
DOI: 10.1126/science.304.5675.1207h

Mutations in the protein parkin, an E3 ubiquitin ligase, cause degeneration of nigrostriatal dopamine neurons and lead to a familial form of Parkinson's disease (PD). Chung et al. (p. 1328, published online 22 April 2004) show that parkin can be S-nitrosylated both in vitro and in vivo and that S-nitrosylation blocks its ubiquitin E3-ligase activity as well as its protective function. The finding that nitrosative stress can impair the function of parkin links a familial form of PD to the more common sporadic form of PD in which nitrosative and oxidative stress are thought to be important factors of pathogenesis.

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