Recent Broad Publications
- A Dietary Regimen of Caloric Restriction or Pharmacological Activation of SIRT1 to Delay the Onset of Neurodegeneration.
Read More / View Supplemental Materials - Synthesis of Stereochemically and Skeletally Diverse Fused Ring Systems from Functionalized C-Glycosides.
Read More / View Supplemental Materials - RhoGTPases - NODes for effector-triggered immunity in animals.
Read More / View Supplemental Materials - Comparative analysis of RNA sequencing methods for degraded or low-input samples.
Read More / View Supplemental Materials - Small-Molecule Inhibitors of Cytokine-Mediated STAT1 Signal Transduction in β-Cells with Improved Aqueous Solubility.
Read More / View Supplemental Materials
Scientific Publications
< Back to Publications
Identification of a small molecule that selectively inhibits alpha-synuclein translational expression
| Publication Type | Journal Article |
| Authors | Ross, NT, Metkar SR, Le H., Burbank J., Cahill C., Germain A., Macpherson L., Bittker J., Palmer M., Rogers J., and Schreiber SL |
| Abstract | Alpha-synuclein is a protein implicated in the pathogenesis of neurodegenerative alpha-synucleinopathies including Parkinson’s disease (PD), the most prevalent movement disorder in humans. Evidence suggests that misregulation of alpha-synuclein translation plays a clear role in the pathology of this disease. Consequently, our therapeutic strategy is to limit alpha-synuclein translation. We report the outcome of a high-throughput chemical library screen to identify novel, nontoxic, and selective small-molecule inhibitors of alpha-synuclein expression, which will aid the development of therapies for PD and other neurodegenerative diseases. Of the 303,224-screened compounds, 36 hits were identified as inhibitors of alpha-synuclein expression and subsequently validated to confirm their inhibitory activity and selectivity. One of these compounds (ML150) displayed greater than 200-fold selective inhibition of alpha-synuclein expression compared with a related system and is inactive in a control system at the highest tested dose. Our results indicate that ML150 has a drug-like structure with no obvious chemical liabilities, excellent solubility, and stability in aqueous conditions. This new probe should be very useful in future cell-based investigations and in vivo studies of alpha-synuclein expression inhibition. |
| Year of Publication | 2012 |
| Date Published (YYYY/MM/DD) | 2012/01/09 |
| PubMed | http://www.ncbi.nlm.nih.gov/pubmed/21634082?dopt=Abstract |
Share This
- Tweet
