High MMP-9 Activity Levels in Fragile X Syndrome are Lowered by Minocycline

作者：Dziembowska Magdalena; Pretto Dalyir I; Janusz Aleksandra; Kaczmarek Leszek; Leigh Mary Jacena; Gabriel Nielsen; Durbin Johnson Blythe; Hagerman Randi J; Tassone Flora^*

来源：American Journal of Medical Genetics, Part A, 2013, 161(8): 1897-1903.

DOI：10.1002/ajmg.a.36023

• minocycline
• FXS
• MMP-9
• metalloproteinases

Fragile X syndrome (FXS) is a neurodevelopmental disorder characterized by lack of the FMR1 protein, FMRP, a translational repressor. Its absence leads to up-regulation of locally translated proteins involved in synaptic transmission and plasticity, including the matrix metalloproteinase-9 (MMP-9). In the Fmr1 knock-out (KO), a mouse model of FXS, an abnormal elevated expression of MMP-9 in the brain was pharmacologically down-regulated after treatment with the tetracycline derivative minocycline. Moreover, the rescue of immature dendritic spine morphology and a significant improvement of abnormal behavior were associated with down-regulation of MMP-9. Here, we report on high plasma activity of MMP-9 in individuals with FXS. In addition, we investigate MMP-9 changes in patients with FXS who have gone through a minocycline controlled clinical trial and correlate MMP-9 activity to clinical observations. The results of this study suggest that, in humans, activity levels of MMP-9 are lowered by minocycline and that, in some cases, changes in MMP-9 at are positively associated with improvement based on clinical measures.

• 出版日期2013-8