Autor: |
Charisse Klaus, Toudjarska Ivanka, Kent Caroline, Hinkle Kelly, Ogholikhan Sina, He Zhen, Braithwaite Adam, Lincoln Sarah, Zehr Cynthia, Hope Andrew, Bumcrot David, Melrose Heather, Lewis Jada, Braich Ravi, Pandey Rajendra K, Heckman Michael, Maraganore Demetrius M, Crook Julia, Farrer Matthew J |
Jazyk: |
angličtina |
Rok vydání: |
2008 |
Předmět: |
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Zdroj: |
Molecular Neurodegeneration, Vol 3, Iss 1, p 19 (2008) |
Druh dokumentu: |
article |
ISSN: |
1750-1326 |
DOI: |
10.1186/1750-1326-3-19 |
Popis: |
Abstract Background Overexpression of α-synuclein (SNCA) in families with multiplication mutations causes parkinsonism and subsequent dementia, characterized by diffuse Lewy Body disease post-mortem. Genetic variability in SNCA contributes to risk of idiopathic Parkinson's disease (PD), possibly as a result of overexpression. SNCA downregulation is therefore a valid therapeutic target for PD. Results We have identified human and murine-specific siRNA molecules which reduce SNCA in vitro. As a proof of concept, we demonstrate that direct infusion of chemically modified (naked), murine-specific siRNA into the hippocampus significantly reduces SNCA levels. Reduction of SNCA in the hippocampus and cortex persists for a minimum of 1 week post-infusion with recovery nearing control levels by 3 weeks post-infusion. Conclusion We have developed naked gene-specific siRNAs that silence expression of SNCA in vivo. This approach may prove beneficial toward our understanding of the endogenous functional equilibrium of SNCA, its role in disease, and eventually as a therapeutic strategy for α-synucleinopathies resulting from SNCA overexpression. |
Databáze: |
Directory of Open Access Journals |
Externí odkaz: |
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