| First Author | Smith WW | Year | 2010 |
| Journal | Hum Mol Genet | Volume | 19 |
| Issue | 11 | Pages | 2087-98 |
| PubMed ID | 20185556 | Mgi Jnum | J:159700 |
| Mgi Id | MGI:4452287 | Doi | 10.1093/hmg/ddq086 |
| Citation | Smith WW, et al. (2010) Synphilin-1 attenuates neuronal degeneration in the A53T alpha-synuclein transgenic mouse model. Hum Mol Genet 19(11):2087-98 |
| abstractText | Genetic alterations in alpha-synuclein cause autosomal dominant familial Parkinsonism and may contribute to sporadic Parkinson's disease (PD). Synphilin-1 is an alpha-synuclein-interacting protein, with implications in PD pathogenesis related to protein aggregation. Currently, the in vivo role of synphilin-1 in alpha-synuclein-linked pathogenesis is not fully understood. Using the mouse prion protein promoter, we generated synphilin-1 transgenic mice, which did not display PD-like phenotypes. However, synphilin-1/A53T alpha-synuclein double-transgenic mice survived longer than A53T alpha-synuclein single-transgenic mice. There were attenuated A53T alpha-synuclein-induced motor abnormalities and decreased astroglial reaction and neuronal degeneration in brains in double-transgenic mice. Overexpression of synphilin-1 decreased caspase-3 activation, increased beclin-1 and LC3 II expression and promoted formation of aggresome-like structures, suggesting that synphilin-1 alters multiple cellular pathways to protect against neuronal degeneration. These studies demonstrate that synphilin-1 can diminish the severity of alpha-synucleinopathy and play a neuroprotective role against A53T alpha-synuclein toxicity in vivo. |
