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Published on: March 24, 2019
α-Synuclein posttranslational modification and alternative splicing as a trigger for neurodegeneration
1Department of Pathology, Hospital Universitari Germans Trias i Pujol, Universitat Autònoma de Barcelona, 08916 Badalona, Barcelona, Spain. katrinbeyer@hotmail.com
Molecular Neurobiology
|August 28, 2012
Summary
Lewy body diseases involve alpha-synuclein (AS) aggregation, influenced by posttranslational modifications and alternative splicing. Understanding these processes is key to the pathogenesis of Parkinson disease and dementia with Lewy bodies.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- Lewy body diseases (LBDs), including Parkinson disease (PD) and dementia with Lewy bodies (DLB), are characterized by alpha-synuclein (AS) aggregates.
- AS aggregation is a central mechanism in LBD pathogenesis.
- AS is a small, soluble protein prone to aggregation, especially when modified.
Purpose of the Study:
- To review the latest insights into alpha-synuclein (AS) posttranslational modifications.
- To elucidate the role of AS modifications in the pathogenesis of Lewy body diseases.
- To examine the implications of AS gene alternative splicing in LBD development.
Main Methods:
- Literature review of studies on AS posttranslational modifications.
- Analysis of AS gene alternative splicing variants.
- Discussion of AS structure-property relationships.
Main Results:
- Posttranslational modifications (phosphorylation, ubiquitination, nitration, truncation) enhance AS aggregation.
- Lewy bodies contain modified forms of AS.
- Alternative splicing of the AS gene generates different protein isoforms with potentially altered aggregation propensities.
Conclusions:
- AS posttranslational modifications and alternative splicing are critical factors in LBD pathogenesis.
- Understanding these molecular mechanisms may lead to new therapeutic strategies for PD and DLB.
- A hypothesis for the development of pure dementia with Lewy bodies is proposed based on AS splicing.
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