Differential aggregation properties of alpha-synuclein isoforms
| Autor: | Silke Appenzeller, W. Völker, Inken Lorenzen, Manuela Pendziwiat, Gregor Kuhlenbäumer, Annika Regulin, May Bungeroth, Joachim Grötzinger |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Gene isoform
Aging Molecular Sequence Data Biology Fibril Protein Aggregation Pathological Protein Aggregates chemistry.chemical_compound In vivo medicine Humans Protein Isoforms Amino Acid Sequence Gene Alpha-synuclein Lewy body General Neuroscience Alternative splicing Brain Parkinson Disease medicine.disease In vitro Cell biology HEK293 Cells chemistry Biochemistry alpha-Synuclein Neurology (clinical) Geriatrics and Gerontology Developmental Biology |
| Zdroj: | Neurobiology of Aging. 35:1913-1919 |
| ISSN: | 0197-4580 |
| Popis: | Pathologic aggregation of α-synuclein is a central process in the pathogenesis of Parkinson's disease. The α-synuclein gene (SNCA) encodes at least 4 different α-synuclein isoforms through alternative splicing (SNCA140, SNCA126, SNCA112, SNCA98). Differential expression of α-synuclein isoforms has been shown in Lewy body diseases. In contrast to the canonical α-synuclein isoform of 140 amino acid residues (SNCA140), which has been investigated in detail, little is known about the properties of the 3 alternative isoforms. We have investigated the aggregation properties of all 4 isoforms in cultured cells and analyzed fibril-formation of 3 isoforms (SNCA140, SNCA126, and SNCA98) in vitro by electron microscopy. Each of the 3 alternative isoforms aggregates significantly less than the canonical isoform SNCA140. Electron microscopy showed that SNCA140 formed the well-known relatively straight fibrils while SNCA126 formed shorter fibrils, which were arranged in parallel fibril bundles and SNCA98 formed annular structures. Expression analysis of α-synuclein isoforms in different human brain regions demonstrated low expression levels of the alternative isoforms in comparison to the canonical SNCA140 isoform. These findings demonstrate that α-synuclein isoforms differ qualitatively and quantitatively in their aggregation properties. The biological consequences of these findings remain to be explored in vitro and in vivo. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect