| First Author | Shimshek DR | Year | 2012 |
| Journal | Sci Rep | Volume | 2 |
| Pages | 262 | PubMed ID | 22355774 |
| Mgi Jnum | J:207278 | Mgi Id | MGI:5555010 |
| Doi | 10.1038/srep00262 | Citation | Shimshek DR, et al. (2012) Excess alpha-synuclein worsens disease in mice lacking ubiquitin carboxy-terminal hydrolase L1. Sci Rep 2:262 |
| abstractText | Mutations in alpha-synuclein (alphaSN) and ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) have been linked to familial Parkinson's disease (PD). Physical and functional interactions between these two proteins have been described. Whether they act additively in vivo to influence disease has remained controversial. alphaSN is a presynaptic protein and the major constituent of Lewy inclusions, histopathological hallmarks of PD. UCH-L1 regulates ubiquitin stability in the nervous system and its loss results in neurodegeneration in peripheral and central neurons. Here, we used genetics to show that UCH-L1-deficiency together with excess alphaSN worsen disease. Double mutant mice show earlier-onset motor deficits, a shorter lifespan and forebrain astrogliosis but the additive disease-worsening effects of UCH-L1-deficiency and excess alphaSN are not accompanied by microgliosis, ubiquitin pathology or changes in pathological alphaSN protein levels and species. |
