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...
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doaj-d9edd2209b2f4d6398bff5ae1997dfc52020-11-24T22:26:01ZengMDPI AGGenes2073-44252018-01-01926310.3390/genes9020063genes9020063Alternative Splicing of Alpha- and Beta-Synuclein Genes Plays Differential Roles in SynucleinopathiesAna Gámez-Valero0Katrin Beyer1Department of Pathology, Germans Trias i Pujol Research Institute, Badalona, 08916 Barcelona, SpainDepartment of Pathology, Germans Trias i Pujol Research Institute, Badalona, 08916 Barcelona, SpainThe 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 SNCA gene, and β-synuclein by SNCB. 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 SNCA, and two in the case of SNCB. Finally, different lengths of 3’ untranslated regions have been also reported for both genes. SNCB only expresses in the brain, but some of the numerous SNCA 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 SNCA and SNCB transcript variants in brain, blood, and non-neuronal tissue of synucleinopathies, but especially PD and DLB as major neurodegenerative disorders.http://www.mdpi.com/2073-4425/9/2/63α-synucleinSNCAβ-synucleinSNCBalternative splicingfunctional splice variantsdifferential expression |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Ana Gámez-Valero Katrin Beyer |
spellingShingle |
Ana Gámez-Valero Katrin Beyer Alternative Splicing of Alpha- and Beta-Synuclein Genes Plays Differential Roles in Synucleinopathies Genes α-synuclein SNCA β-synuclein SNCB alternative splicing functional splice variants differential expression |
author_facet |
Ana Gámez-Valero Katrin Beyer |
author_sort |
Ana Gámez-Valero |
title |
Alternative Splicing of Alpha- and Beta-Synuclein Genes Plays Differential Roles in Synucleinopathies |
title_short |
Alternative Splicing of Alpha- and Beta-Synuclein Genes Plays Differential Roles in Synucleinopathies |
title_full |
Alternative Splicing of Alpha- and Beta-Synuclein Genes Plays Differential Roles in Synucleinopathies |
title_fullStr |
Alternative Splicing of Alpha- and Beta-Synuclein Genes Plays Differential Roles in Synucleinopathies |
title_full_unstemmed |
Alternative Splicing of Alpha- and Beta-Synuclein Genes Plays Differential Roles in Synucleinopathies |
title_sort |
alternative splicing of alpha- and beta-synuclein genes plays differential roles in synucleinopathies |
publisher |
MDPI AG |
series |
Genes |
issn |
2073-4425 |
publishDate |
2018-01-01 |
description |
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 SNCA gene, and β-synuclein by SNCB. 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 SNCA, and two in the case of SNCB. Finally, different lengths of 3’ untranslated regions have been also reported for both genes. SNCB only expresses in the brain, but some of the numerous SNCA 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 SNCA and SNCB transcript variants in brain, blood, and non-neuronal tissue of synucleinopathies, but especially PD and DLB as major neurodegenerative disorders. |
topic |
α-synuclein SNCA β-synuclein SNCB alternative splicing functional splice variants differential expression |
url |
http://www.mdpi.com/2073-4425/9/2/63 |
work_keys_str_mv |
AT anagamezvalero alternativesplicingofalphaandbetasynucleingenesplaysdifferentialrolesinsynucleinopathies AT katrinbeyer alternativesplicingofalphaandbetasynucleingenesplaysdifferentialrolesinsynucleinopathies |
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