| First Author | Sardi SP | Year | 2011 |
| Journal | Proc Natl Acad Sci U S A | Volume | 108 |
| Issue | 29 | Pages | 12101-6 |
| PubMed ID | 21730160 | Mgi Jnum | J:174360 |
| Mgi Id | MGI:5085930 | Doi | 10.1073/pnas.1108197108 |
| Citation | Sardi SP, et al. (2011) CNS expression of glucocerebrosidase corrects {alpha}-synuclein pathology and memory in a mouse model of Gaucher-related synucleinopathy. Proc Natl Acad Sci U S A 108(29):12101-6 |
| abstractText | Emerging genetic and clinical evidence suggests a link between Gaucher disease and the synucleinopathies Parkinson disease and dementia with Lewy bodies. Here, we provide evidence that a mouse model of Gaucher disease (Gba1(D409V/D409V)) exhibits characteristics of synucleinopathies, including progressive accumulation of proteinase K-resistant alpha-synuclein/ubiquitin aggregates in hippocampal neurons and a coincident memory deficit. Analysis of homozygous (Gba1(D409V/D409V)) and heterozygous (Gba1(D409V/+) and Gba1(+/-)) Gaucher mice indicated that these pathologies are a result of the combination of a loss of glucocerebrosidase activity and a toxic gain-of-function resulting from expression of the mutant enzyme. Importantly, adeno-associated virus-mediated expression of exogenous glucocerebrosidase injected into the hippocampus of Gba1(D409V/D409V) mice ameliorated both the histopathological and memory aberrations. The data support the contention that mutations in GBA1 can cause Parkinson disease-like alpha-synuclein pathology, and that rescuing brain glucocerebrosidase activity might represent a therapeutic strategy for GBA1-associated synucleinopathies. |
