| First Author | Fujita M | Year | 2010 |
| Journal | Nat Commun | Volume | 1 |
| Pages | 110 | PubMed ID | 21045828 |
| Mgi Jnum | J:220941 | Mgi Id | MGI:5637487 |
| Doi | 10.1038/ncomms1101 | Citation | Fujita M, et al. (2010) A beta-synuclein mutation linked to dementia produces neurodegeneration when expressed in mouse brain. Nat Commun 1:110 |
| abstractText | The discovery of alpha-synuclein (alphaS) mutations has made a major contribution to the understanding of the pathogenesis of alpha-synucleinopathies such as Parkinson's disease and dementia with Lewy bodies (DLB). In contrast, less attention has been paid to beta-synuclein (betaS) mutations. In this paper, we show that transgenic (tg) mice expressing DLB-linked P123H betaS develop progressive neurodegeneration, as characterized by axonal swelling, astrogliosis and behavioural abnormalities, with memory disorder being more prominent than motor deficits. Furthermore, cross-breeding of P123H betaS tg mice with alphaS tg mice, but not with alphaS knockout mice, greatly enhanced neurodegeneration phenotypes. These results suggest that P123H betaS is pathogenic and cooperates with pathogenic alphaS to stimulate neurodegeneration in mouse brain, indicating a causative role of P123H betaS in familial DLB. Given the neuritic pathology of betaS in sporadic alpha-synucleinopathies, it appears that alteration of betaS can contribute to the pathogenesis of a broad range of alpha-synucleinopathies. |
