Title |
In vivo silencing of alpha-synuclein using naked siRNA
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Published in |
Molecular Neurodegeneration, November 2008
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DOI | 10.1186/1750-1326-3-19 |
Pubmed ID | |
Authors |
Jada Lewis, Heather Melrose, David Bumcrot, Andrew Hope, Cynthia Zehr, Sarah Lincoln, Adam Braithwaite, Zhen He, Sina Ogholikhan, Kelly Hinkle, Caroline Kent, Ivanka Toudjarska, Klaus Charisse, Ravi Braich, Rajendra K Pandey, Michael Heckman, Demetrius M Maraganore, Julia Crook, Matthew J Farrer |
Abstract |
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. 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. 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. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 1 | 100% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 1 | 100% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 2 | 1% |
Unknown | 152 | 99% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 24 | 16% |
Student > Master | 22 | 14% |
Student > Bachelor | 20 | 13% |
Researcher | 20 | 13% |
Other | 10 | 6% |
Other | 21 | 14% |
Unknown | 37 | 24% |
Readers by discipline | Count | As % |
---|---|---|
Agricultural and Biological Sciences | 35 | 23% |
Biochemistry, Genetics and Molecular Biology | 25 | 16% |
Neuroscience | 20 | 13% |
Medicine and Dentistry | 10 | 6% |
Pharmacology, Toxicology and Pharmaceutical Science | 8 | 5% |
Other | 15 | 10% |
Unknown | 41 | 27% |