MMP inhibitors as potential anti-epileptogenic therapeutics

 

 

 

MMPs are either secreted or membrane-bound extracellularly operating proteases. Most of them are released in a latent form, with a propeptide covering the enzymatic active site. Hence, the removal of the propeptide that occurs outside the cells is an important step in revealing the enzymatic activity. Potential involvement of MMP-9 in the epileptogenesis has been suggested by us and others first by its activation by the seizure-evoking stimuli, and then confirmed in either knockout or overexpressing transgenic rodents. Recently, we have also observed activation of MMP-9 in clinically relevant model of traumatic brain injury-evoked epileptogenesis. In this project, we hypothesize that sustained MMP-9 increases contribute to aberrant plasticity underlying epileptogenesis. Therefore, we propose that brain-penetrating inhibitors of MMP-9 may be effective as novel class of therapeutic agents against epileptogenesis. This project will use neurophysiological, histopathological and molecular methods to address this.

 

 

Supervisor: Leszek Kaczmarek (or someone with similar expertise)

To apply :

 https://recruitment.nencki.gov.pl/register.php?call=ecmed2015