| First Author | Nakayama K | Year | 2009 |
| Journal | Am J Pathol | Volume | 174 |
| Issue | 4 | Pages | 1471-80 |
| PubMed ID | 19286568 | Mgi Jnum | J:147053 |
| Mgi Id | MGI:3839173 | Doi | 10.2353/ajpath.2009.080503 |
| Citation | Nakayama K, et al. (2009) Microtubule depolymerization suppresses alpha-synuclein accumulation in a mouse model of multiple system atrophy. Am J Pathol 174(4):1471-80 |
| abstractText | Multiple system atrophy (MSA) is a neurodegenerative disease caused by an accumulation of alpha-synuclein (alpha-syn) in oligodendrocytes. Little is known about the cellular mechanisms by which alpha-syn accumulation causes neuronal degeneration in MSA. Our previous research, however, revealed that in a mouse model of MSA, oligodendrocytic inclusions of alpha-syn induced neuronal accumulation of alpha-syn, as well as progressive neuronal degeneration. Here we identify the mechanisms that underlie neuronal accumulation of alpha-syn in a mouse MSA model. We found that the alpha-syn protein binds to beta-III tubulin in microtubules to form an insoluble complex. The insoluble alpha-syn complex progressively accumulates in neurons and leads to neuronal dysfunction. Furthermore, we demonstrated that the neuronal accumulation of insoluble alpha-syn is suppressed by treatment with a microtubule depolymerizing agent. The underlying pathological process appeared to also be inhibited by this treatment, providing promise for future therapeutic approaches. |
