| First Author | Doxakis E | Year | 2010 |
| Journal | J Biol Chem | Volume | 285 |
| Issue | 17 | Pages | 12726-34 |
| PubMed ID | 20106983 | Mgi Jnum | J:165946 |
| Mgi Id | MGI:4838955 | Doi | 10.1074/jbc.M109.086827 |
| Citation | Doxakis E (2010) Post-transcriptional regulation of alpha-synuclein expression by mir-7 and mir-153. J Biol Chem 285(17):12726-34 |
| abstractText | Genetic and biochemical studies have established a central role for alpha-synuclein accumulation in the pathogenesis of Parkinson disease. Here, two microRNAs, namely mir-7 and mir-153, have been identified to regulate alpha-synuclein levels post-transcriptionally. These microRNAs bind specifically to the 3'-untranslated region of alpha-synuclein and down-regulate its mRNA and protein levels, with their effect being additive. They are expressed predominantly in the brain with a pattern that mirrors synuclein expression in different tissues as well as during neuronal development, indicating that they play a tuning role in the amount of alpha-synuclein produced. Overexpression of mir-7 and mir-153 significantly reduces endogenous alpha-synuclein levels, whereas inhibition of mir-7 and mir-153 enhances translation of a luciferase construct bearing the alpha-synuclein 3'-untranslated region in primary neurons. These findings reveal a significant additional mechanism by which alpha-synuclein is regulated and point toward new therapeutic regimes for lowering endogenous alpha-synuclein levels in patients with familial or sporadic Parkinson disease. |
