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Mutation analysis of the seven in absentia homolog 1 (SIAH1) gene in Parkinson’s disease

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Summary.

Seven in absentia homolog 1 (SIAH-1) is a member of the RING-finger-containing E3 ubiquitin ligases. Two substrates of SIAH-1 are α-synuclein and synphilin-1, both of these proteins are involved in Parkinson’s disease (PD). Recently, mutations in Parkin, another E3 ubiquitin ligase which ubiquinates synphilin-1 and glycosylated α-synuclein, have been defined as a major cause of autosomal recessive PD. The potential role of SIAH-1 in PD is further underlined as SIAH-1 protein is a component of the Lewy bodies and as it plays a role in apoptosis caused by nitric oxide (NO) induced oxidative stress. Thus, we performed a mutation screening of the SIAH-1 gene in PD patients. However, screening a large sample of 209 familial and sporadic PD patients we could not find any disease causing mutation. We therefore conclude that genetic alterations of SIAH-1 do not significantly contribute to the pathogenesis of PD.

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Authors and Affiliations

  1. Department of Medical Genetics, University of Tuebingen, Tuebingen, Germany

    T. Franck & O. Riess

  2. Center of Neurology and Hertie Institute for Brain Research, University of Tuebingen, Tuebingen, Germany

    R. Krueger

  3. Department of Neurology, Ruhr-University Bochum, Bochum, Germany

    D. Woitalla & T. Müller

  4. Department of Pharmacology, The Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel

    S. Engelender

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  1. T. Franck
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Franck, T., Krueger, R., Woitalla, D. et al. Mutation analysis of the seven in absentia homolog 1 (SIAH1) gene in Parkinson’s disease. J Neural Transm 113, 1903–1908 (2006). https://doi.org/10.1007/s00702-006-0480-z

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