Ontology highlight
ABSTRACT: Background
Overexpression of alpha-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 alpha-synucleinopathies resulting from SNCA overexpression.
SUBMITTER: Lewis J
PROVIDER: S-EPMC2612658 | biostudies-literature | 2008 Nov
REPOSITORIES: biostudies-literature
Lewis Jada J Melrose Heather H Bumcrot David D Hope Andrew A Zehr Cynthia C Lincoln Sarah S Braithwaite Adam A He Zhen Z Ogholikhan Sina S Hinkle Kelly K Kent Caroline C Toudjarska Ivanka I Charisse Klaus K Braich Ravi R Pandey Rajendra K RK Heckman Michael M Maraganore Demetrius M DM Crook Julia J Farrer Matthew J MJ
Molecular neurodegeneration 20081101
<h4>Background</h4>Overexpression of alpha-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.<h4>Results</h4>We have identified human and murine-specific siRNA molecules which reduce SNCA in vitr ...[more]