Abstract
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 activity are positively associated with improvement based on clinical measures.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1897-1903 |
| Number of pages | 7 |
| Journal | American Journal of Medical Genetics, Part A |
| Volume | 161 |
| Issue number | 8 |
| DOIs | |
| State | Published - Aug 2013 |
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Keywords
- FXS
- Metalloproteinases
- Minocycline
- MMP-9
ASJC Scopus subject areas
- Genetics(clinical)
- Genetics
Cite this
High MMP-9 activity levels in fragile X syndrome are lowered by minocycline. / Dziembowska, Magdalena; Pretto, Dalyir I.; Janusz, Aleksandra; Kaczmarek, Leszek; Leigh, Mary Jacena; Gabriel, Nielsen; Durbin-Johnson, Blythe; Hagerman, Randi J; Tassone, Flora.
In: American Journal of Medical Genetics, Part A, Vol. 161, No. 8, 08.2013, p. 1897-1903.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - High MMP-9 activity levels in fragile X syndrome are lowered by minocycline
AU - Dziembowska, Magdalena
AU - Pretto, Dalyir I.
AU - Janusz, Aleksandra
AU - Kaczmarek, Leszek
AU - Leigh, Mary Jacena
AU - Gabriel, Nielsen
AU - Durbin-Johnson, Blythe
AU - Hagerman, Randi J
AU - Tassone, Flora
PY - 2013/8
Y1 - 2013/8
N2 - 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 activity are positively associated with improvement based on clinical measures.
AB - 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 activity are positively associated with improvement based on clinical measures.
KW - FXS
KW - Metalloproteinases
KW - Minocycline
KW - MMP-9
UR - http://www.scopus.com/inward/record.url?scp=84880746947&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84880746947&partnerID=8YFLogxK
U2 - 10.1002/ajmg.a.36023
DO - 10.1002/ajmg.a.36023
M3 - Article
C2 - 23824974
AN - SCOPUS:84880746947
VL - 161
SP - 1897
EP - 1903
JO - American Journal of Medical Genetics
JF - American Journal of Medical Genetics
SN - 1552-4825
IS - 8
ER -