β-III Tubulin Fragments Inhibit α-Synuclein Accumulation in Models of Multiple System Atrophy
| Autor: | Yasuyo Suzuki, Tamaki Iwase, Chenghua Jin, Ikuru Yazawa |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Genetically modified mouse
animal diseases Mice Transgenic Plasma protein binding Protein aggregation Biochemistry Protein–protein interaction Mice chemistry.chemical_compound Atrophy Tubulin mental disorders medicine Animals Molecular Biology Cells Cultured DNA Primers Neurons Alpha-synuclein Base Sequence biology Neurodegeneration Molecular Bases of Disease Cell Biology Multiple System Atrophy medicine.disease Molecular biology nervous system diseases Disease Models Animal nervous system chemistry alpha-Synuclein biology.protein Protein Binding |
| Zdroj: | Journal of Biological Chemistry. 289:24374-24382 |
| ISSN: | 0021-9258 |
| Popis: | Multiple system atrophy (MSA) is a neurodegenerative disease caused by α-synuclein aggregation in oligodendrocytes and neurons. Using a transgenic mouse model overexpressing human α-synuclein in oligodendrocytes, we previously demonstrated that oligodendrocytic α-synuclein inclusions induce neuronal α-synuclein accumulation and progressive neuronal degeneration. α-Synuclein binds to β-III tubulin, leading to the neuronal accumulation of insoluble α-synuclein in an MSA mouse model. The present study demonstrates that α-synuclein co-localizes with β-III tubulin in the brain tissue from patients with MSA and MSA model transgenic mice as well as neurons cultured from these mice. Accumulation of insoluble α-synuclein in MSA mouse neurons was blocked by the peptide fragment β-III tubulin (residues 235-282). We have determined the α-synuclein-binding domain of β-III tubulin and demonstrated that a short fragment containing this domain can suppress α-synuclein accumulation in the primary cultured cells. Administration of a short α-synuclein-binding fragment of β-III tubulin may be a novel therapeutic strategy for MSA. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|