Alternative Splicing of Alpha- and Beta-Synuclein Genes Plays Differential Roles in Synucleinopathies.

The synuclein family is composed of three members, two of which, α- and β-synuclein, play a major role in the development of synucleinopathies, including Parkinson's disease (PD) as most important movement disorder, dementia with Lewy bodies (DLB) as the second most frequent cause of dementia after Alzheimer's disease and multiple system atrophy. Whereas abnormal oligomerization and fibrillation of α-synuclein are now well recognized as initial steps in the development of synucleinopathies, β-synuclein is thought to be a natural α-synuclein anti-aggregant. α-synuclein is encoded by the gene, and β-synuclein by . Both genes are homologous and undergo complex splicing events. On one hand, in-frame splicing of coding exons gives rise to at least three shorter transcripts, and the functional properties of the corresponding protein isoforms are different. Another type of alternative splicing is the alternative inclusion of at least four initial exons in the case of , and two in the case of . Finally, different lengths of 3' untranslated regions have been also reported for both genes. only expresses in the brain, but some of the numerous transcripts are also brain-specific. With the present article, we aim to provide a systematic review of disease related changes in the differential expression of the various and transcript variants in brain, blood, and non-neuronal tissue of synucleinopathies, but especially PD and DLB as major neurodegenerative disorders.