Identification and characterization of a new alpha-synuclein isoform and its role in Lewy body diseases

Katrin Beyer, Montserrat Domingo-Sábat, José I. Lao, Cristina Carrato, Isidro Ferrer, Aurelio Ariza

Research output: Contribution to journalArticleResearchpeer-review

57 Citations (Scopus)

Abstract

Alternative splicing is an important mechanism to generate a large number of mRNAs, thus increasing proteome diversity and tissue specificity. Three transcript variants of alpha-synuclein, a neuronal protein mainly involved in synapses, have been described so far. Whereas alpha-synuclein 140 is the whole and main transcript, alpha-synuclein 112 and 126 are short proteins that result from in-frame deletions of exons 3 and 5, respectively. Because the aforesaid alpha-synuclein isoforms show differential expression changes in Lewy body diseases (LBDs), in the present work, we searched for a fourth alpha-synuclein isoform and studied its expression levels in LBD brains. By using isoform-specific primers, isoform co-amplification and direct sequencing, we identified alpha-synuclein 98, which lacks exons 3 and 5. mRNA expression analyses in non-neuronal tissue revealed that alpha-synuclein 98 is a brain-specific splice variant with varying expression levels in different areas of fetal and adult brain. Additionally, we studied alpha-synuclein 98 expression levels by real-time semi-quantitative RT-PCR in the frontal cortices of LBD patients and compared them with those of Alzheimer disease (AD) patients and control subjects. Overexpression of alpha-synuclein 98 in LBD and AD brains would indicate its specific involvement in the pathogenesis of these neurodegenerative disorders. © 2007 Springer-Verlag.
Original languageEnglish
Pages (from-to)15-23
JournalNeurogenetics
Volume9
Issue number1
DOIs
Publication statusPublished - 1 Feb 2008

Keywords

  • Alpha-synuclein
  • Alzheimer disease
  • Dementia with Lewy bodies
  • Differential isoform expression
  • mRNA expression

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