By C. L. Wellington, B. R. Leavitt (auth.), Prof. Y. Mizuno, Prof. D. B. Calne, Dr. R. Horowski, Prof. W. Poewe, Prof. P. Riederer, Prof. M. B. H. Youdim (eds.)
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Additional resources for Advances in Research on Neurodegeneration: Volume 7
This mutation was shown to reduce the enzymatic activity of ubiquitine hydrolase in vitro. Although the physiologic role of this enzyme is not entirely clear, it may be involved in the recycling of ubiquitine from ubiquitinized proteins, and thus it can be hypothesized that a reduction in its activity may in some way contribute to a disturbance of protein degradation and consequently to intracellular protein aggregation. The observation is interesting, as it again implicates cellular ubiquitination/protein degradation mechanisms.
No common mutations were found among the affected families and sites of mutations were different along the Parkin gene, indicating the genetic heterogeneity of AR-1P and many founders of Parkin mutations. Also, many of these affected families are not consanguineous and hence there may be many carriers of AR-JP in Japan. In the remaining affected AR-1P families (30%), no homozygous mutations were found in the coding regions of Parkin gene. These patients may have mutations in the upstream regulatory region, or intron sequences of the Parkin gene.
Nature Genet 18: 106-108 Lazzarini AM, Myers RH , Zimmerman TR Jr, Mark MH, Golbe LI, Sage n, Johnson WG, Duvoisin RC (1994) A clinical genetic study of Parkinson's disease: evidence for dominant transmission. Neurology 44: 499-506 Leroy E, Boyer R, Auburger G, Leube B, Ulm G , Mezey E , Harta G, Brownstein MJ, Jonnalagada S, Chernova T, Dehejia A, Lavedan C, Gasser T, Steinbach PJ, Wilkinson KO , Polymeropoulos MH (1998) The ubiquitin pathway in Parkinson's disease. Nature 395: 451-452 Lippa CF, Fujiwara H, Mann DM, Giasson B, Baba M, Schmidt ML, Nee LE, O 'Connell B, Pollen DA, St.
Advances in Research on Neurodegeneration: Volume 7 by C. L. Wellington, B. R. Leavitt (auth.), Prof. Y. Mizuno, Prof. D. B. Calne, Dr. R. Horowski, Prof. W. Poewe, Prof. P. Riederer, Prof. M. B. H. Youdim (eds.)