Sterne Gabriella R, Kim Jung Hwan, Ye Bing
Life Sciences Institute, University of Michigan, Ann Arbor, United States.
Elife. 2015 May 19;4:e05196. doi: 10.7554/eLife.05196.
Increased expression of Down Syndrome Cell Adhesion Molecule (Dscam) is implicated in the pathogenesis of brain disorders such as Down syndrome (DS) and fragile X syndrome (FXS). Here, we show that the cellular defects caused by dysregulated Dscam levels can be ameliorated by genetic and pharmacological inhibition of Abelson kinase (Abl) both in Dscam-overexpressing neurons and in a Drosophila model of fragile X syndrome. This study offers Abl as a potential therapeutic target for treating brain disorders associated with dysregulated Dscam expression.
唐氏综合征细胞粘附分子(Dscam)表达增加与诸如唐氏综合征(DS)和脆性X综合征(FXS)等脑部疾病的发病机制有关。在此,我们表明,在Dscam过表达的神经元以及脆性X综合征的果蝇模型中,通过阿贝尔森激酶(Abl)的基因和药理学抑制,可改善由Dscam水平失调引起的细胞缺陷。本研究提出Abl作为治疗与Dscam表达失调相关脑部疾病的潜在治疗靶点。