| First Author | Suzuki Y | Year | 2014 |
| Journal | J Biol Chem | Volume | 289 |
| Issue | 35 | Pages | 24374-82 |
| PubMed ID | 25028513 | Mgi Jnum | J:317643 |
| Mgi Id | MGI:6855712 | Doi | 10.1074/jbc.M114.557215 |
| Citation | Suzuki Y, et al. (2014) beta-III Tubulin fragments inhibit alpha-synuclein accumulation in models of multiple system atrophy. J Biol Chem 289(35):24374-82 |
| abstractText | Multiple system atrophy (MSA) is a neurodegenerative disease caused by alpha-synuclein aggregation in oligodendrocytes and neurons. Using a transgenic mouse model overexpressing human alpha-synuclein in oligodendrocytes, we previously demonstrated that oligodendrocytic alpha-synuclein inclusions induce neuronal alpha-synuclein accumulation and progressive neuronal degeneration. alpha-Synuclein binds to beta-III tubulin, leading to the neuronal accumulation of insoluble alpha-synuclein in an MSA mouse model. The present study demonstrates that alpha-synuclein co-localizes with beta-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 alpha-synuclein in MSA mouse neurons was blocked by the peptide fragment beta-III tubulin (residues 235-282). We have determined the alpha-synuclein-binding domain of beta-III tubulin and demonstrated that a short fragment containing this domain can suppress alpha-synuclein accumulation in the primary cultured cells. Administration of a short alpha-synuclein-binding fragment of beta-III tubulin may be a novel therapeutic strategy for MSA. |
