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Differential expression of alpha-synuclein, parkin, and synphilin-1 isoforms in Lewy body disease

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Abstract

Alpha-synuclein, parkin, and synphilin-1 are proteins mainly involved in the pathogenesis of Lewy body (LB) diseases. mRNAs of all three undergo alternative splicing, so that the existence of various isoforms has been described. Since increasing evidence supports the importance of differential isoform-expression changes in disease development, we have established isoform-expression profiles in frontal cortices of LB disease brains in comparison with those of Alzheimer disease (AD) and control frontal cortices. The differential expression of four alpha-synuclein, seven parkin, and four synphilin-1 isoforms was ascertained by the use of isoform-specific primers and relative expression analysis with SybrGreen and beta-actin as an internal standard. The establishment of isoform-expression profiles revealed that these are disease specific. Moreover, isoform-expression deregulation of mainly one gene in each disease could be observed. All four alpha-synuclein isoforms were affected in the case of the pure form of dementia with LB, most parkin transcript variants in common LB disease, and all synphilin-1 isoforms in Parkinson disease. Only minor involvement was detected in AD. Finally, the existence of a proprietary isoform-expression profile in common LB disease indicates that this disease develops as a result of its own molecular mechanisms, and so, at the molecular level, it does not exactly share changes found in pure dementia with LB and AD. In conclusion, isoform-expression profiles in LB diseases represent additional evidence for the direct involvement of isoform-expression deregulation in the development of neurodegenerative disorders.

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Acknowledgments

We thank the University of Barcelona and Institute of Neuropathology Brain Banks, Barcelona, Spain, for their help with tissue procurement. We thank T. Jonahann for his editorial help. This work was supported by Spain’s Ministry of Health FIS grants PI 030132 and PI 050867, Catalonia’s AGAUR grant 2005SGR828, and MaratóTV3 grant 06/1410.

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Authors and Affiliations

  1. Department of Pathology, Hospital Germans Trias i Pujol, Autonomous University of Barcelona, 08916 Badalona, Barcelona, Spain

    Katrin Beyer, Montserrat Domingo-Sàbat, Jordi Humbert, Cristina Carrato & Aurelio Ariza

  2. Institute of Neuropathology, Hospital de Bellvitge, L’Hospitalet de Llobregat, Spain

    Isidro Ferrer

  3. ICS Institute of Neuropathology, Barcelona, Spain

    Katrin Beyer, Cristina Carrato, Isidro Ferrer & Aurelio Ariza

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  1. Katrin Beyer
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  2. Montserrat Domingo-Sàbat
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  3. Jordi Humbert
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  4. Cristina Carrato
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  5. Isidro Ferrer
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Correspondence to Katrin Beyer.

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Beyer, K., Domingo-Sàbat, M., Humbert, J. et al. Differential expression of alpha-synuclein, parkin, and synphilin-1 isoforms in Lewy body disease. Neurogenetics 9, 163–172 (2008). https://doi.org/10.1007/s10048-008-0124-6

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  • DOI: https://doi.org/10.1007/s10048-008-0124-6

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