| First Author | Fan Y | Year | 2006 |
| Journal | Hum Mol Genet | Volume | 15 |
| Issue | 20 | Pages | 3002-11 |
| PubMed ID | 16959793 | Mgi Jnum | J:115164 |
| Mgi Id | MGI:3690800 | Doi | 10.1093/hmg/ddl242 |
| Citation | Fan Y, et al. (2006) Beta-synuclein modulates alpha-synuclein neurotoxicity by reducing alpha-synuclein protein expression. Hum Mol Genet 15(20):3002-11 |
| abstractText | Parkinson's disease (PD) is a neurodegenerative disorder characterized by fibrillar aggregates of alpha-synuclein in characteristic inclusions known as 'Lewy bodies'. As mutations altering alpha-synuclein structure or increasing alpha-synuclein expression level can cause familial forms of PD or related Lewy body disorders, alpha-synuclein is believed to play a central role in the process of neuron toxicity, degeneration and death in 'synucleinopathies'. beta-synuclein is closely related to alpha-synuclein and has been shown to inhibit alpha-synuclein aggregation and ameliorate alpha-synuclein neurotoxicity. We generated beta-synuclein transgenic mice and observed a marked reduction in alpha-synuclein protein expression in the cortex of mice over-expressing beta-synuclein. This reduction in alpha-synuclein protein expression was not accompanied by decreases in alpha-synuclein mRNA expression. Using the prion protein promoter alpha-synuclein A53T mouse model of PD, we demonstrated that over-expression of beta-synuclein could retard the progression of impaired motor performance, reduce alpha-synuclein aggregation and extend survival in doubly transgenic mice. We attributed the amelioration of alpha-synuclein neurotoxicity in such bigenic mice to the ability of beta-synuclein to reduce alpha-synuclein protein expression based upon I(125) autoradiography quantification. Our findings indicate that increased expression of beta-synuclein protein results in a reduction of alpha-synuclein protein expression. As increased expression of alpha-synuclein may cause or contribute to PD pathogenesis in sporadic and familial forms of disease, this observation has important implications for the development of therapies for PD. |
