Acta Neuropathologica

, Volume 112, Issue 3, pp 237–251 | Cite as

α-Synuclein structure, posttranslational modification and alternative splicing as aggregation enhancers

  • Katrin BeyerEmail author


α-Synuclein aggregation is thought to be a key event in the pathogenesis of synucleinopathies. Although different α-synuclein alterations and modifications have been proposed to be responsible for early aggregation steps, the mechanisms underlying these events remain unclarified. α-Synuclein is a small protein localized to synaptic terminals and its intrinsic structure has been claimed to be an important factor for self-oligomerization and self-aggregation. α-Synuclein expression studies in cell cultures have demonstrated that posttranslational modifications, such as phosphorylation, oxidation, and sumoylation, are primarily involved in α-synuclein aggregation. Furthermore, in the last few years accumulating evidence has pointed to alternative splicing as a crucial mechanism in the development of neurodegenerative disorders. At least three different α-synuclein isoforms have been described as products of alternative splicing. Two of these isoforms (α-synuclein 112 and α-synuclein 126) are shorter proteins with probably altered functions and aggregation propensity. The present review attempts to summarize the data so far available on α-synuclein structure, posttranslational modifications, and alternative splicing as possible enhancers of aggregation.


α-Synuclein Aggregation Alternative splicing Posttranslational modifications 



This study was supported by FIS Grants PI030132 and PI050867. I thank Professor Aurelio Ariza and Doctor José I. Lao for their critical reading of the manuscript and their commentaries and recommendations.


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© Springer-Verlag 2006

Authors and Affiliations

  1. 1.Department of PathologyHospital Universitari Germans Trias i Pujol, Autonomous University of BarcelonaBadalonaSpain

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