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Hara, Makoto R.; Thomas, Bobby; Cascio, Matthew B.; Bae, Byoung-II; Hester, Lynda D.; Dawson, Valina L.; Dawson, Ted M.; Sawa, Akira; Snyder, Solomon H.
Proceedings of the National Academy of Sciences - PNAS, 03/2006, Letnik: 103, Številka: 10Journal Article
Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) participates in a cell death cascade wherein a variety of stimuli activate nitric oxide (NO) synthases with NO nitrosylating GAPDH, conferring on it the ability to bind to Siah, an E3-ubiquitin-ligase, whose nuclear localization signal enables the GAPDH/Siah protein complex to translocate to the nucleus where degradation of Siah targets elicits cell death. R-(-)-Deprenyl (deprenyl) ameliorates the progression of disability in early Parkinson's disease and also has neuroprotective actions. We show that deprenyl and a related agent, TCH346, in subnanomolar concentrations, prevent S-nitrosylation of GAPDH, the binding of GAPDH to Siah, and nuclear translocation of GAPDH. In mice treated with the dopamine neuronal toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), low doses of deprenyl prevent binding of GAPDH and Siahl in the dopamineenriched corpus striatum.
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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in: SICRIS
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