Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, 6, Avenue du Swing, 4367, Belvaux, Luxembourg.
Mol Neurobiol. 2018 Apr;55(4):3490-3498. doi: 10.1007/s12035-017-0570-y. Epub 2017 May 15.
Parkinson's disease (PD) is the second most common neurodegenerative disorder. Accumulating evidences suggest that PD might have a strong neurodevelopmental component. Among the genetic cases, mutations in the leucine-rich repeat kinase 2 (LRRK2) are well known to be disease causing. Although the molecular mechanism of the pathogenic LRRK2 function is not fully clear, inhibition of microRNA (miRNA) activity has been suggested to be among the pathogenic LRRK2 targets. Here, we demonstrate that the miRNA activity inhibition function of pathogenic LRRK2 is directly antagonized by the neuronal cell fate determinant TRIM32. These findings suggest that TRIM32 might be a modifier for PD and could be a novel therapeutic target.
帕金森病（PD）是第二常见的神经退行性疾病。越来越多的证据表明，PD 可能具有很强的神经发育成分。在遗传病例中，富含亮氨酸重复激酶 2（LRRK2）的突变被认为是致病的。尽管致病 LRRK2 功能的分子机制尚不完全清楚，但抑制 microRNA（miRNA）活性已被认为是致病 LRRK2 的靶点之一。在这里，我们证明了致病 LRRK2 的 miRNA 活性抑制功能直接受到神经元细胞命运决定因子 TRIM32 的拮抗。这些发现表明，TRIM32 可能是 PD 的修饰因子，也可能是一个新的治疗靶点。
