DP-b99 modulates matrix metalloproteinase activity and neuronal plasticity

Marine Yeghiazaryan, Izabela Rutkowska-Wlodarczyk, Anna Konopka, Grzegorz M Wilczyński, Armenuhi Melikyan, Eduard Korkotian, Leszek Kaczmarek, Izabela Figiel

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

DP-b99 is a membrane-activated chelator of zinc and calcium ions, recently proposed as a therapeutic agent. Matrix metalloproteinases (MMPs) are zinc-dependent extracellularly operating proteases that might contribute to synaptic plasticity, learning and memory under physiological conditions. In excessive amounts these enzymes contribute to a number of neuronal pathologies ranging from the stroke to neurodegeneration and epileptogenesis. In the present study, we report that DP-b99 delays onset and severity of PTZ-induced seizures in mice, as well as displays neuroprotective effect on kainate excitotoxicity in hippocampal organotypic slices and furthermore blocks morphological reorganization of the dendritic spines evoked by a major neuronal MMP, MMP-9. Taken together, our findings suggest that DP-b99 may inhibit neuronal plasticity driven by MMPs, in particular MMP-9, and thus may be considered as a therapeutic agent under conditions of aberrant plasticity, such as those subserving epileptogenesis.

Original languageEnglish
Article numbere99789
Pages (from-to)1-9
Number of pages9
JournalPLoS ONE
Volume9
Issue number6
DOIs
Publication statusPublished - 11 Jun 2014
Externally publishedYes

Keywords

  • Animals
  • Chelating Agents
  • Dendritic Spines
  • Egtazic Acid
  • Hippocampus
  • Kainic Acid
  • Male
  • Matrix Metalloproteinase 9
  • Mice
  • Mice, Inbred C57BL
  • Neuronal Plasticity
  • Seizures
  • Journal Article
  • Research Support, Non-U.S. Gov't

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