Neural ECM proteases in learning and synaptic plasticity

Effie Tsilibary, Athina Tzinia, Lidija Radenovic, Vera Stamenkovic, Tomasz Lebitko, Mariusz Mucha, Robert Pawlak, Renato Frischknecht, Leszek Kaczmarek

Research output: Contribution to journalArticlepeer-review

39 Scopus citations


Recent studies implicate extracellular proteases in synaptic plasticity, learning, and memory. The data are especially strong for such serine proteases as thrombin, tissue plasminogen activator, neurotrypsin, and neuropsin as well as matrix metalloproteinases, MMP-9 in particular. The role of those enzymes in the aforementioned phenomena is supported by the experimental results on the expression patterns (at the gene expression and protein and enzymatic activity levels) and functional studies, including knockout mice, specific inhibitors, etc. Counterintuitively, the studies have shown that the extracellular proteolysis is not responsible mainly for an overall degradation of the extracellular matrix (ECM) and loosening perisynaptic structures, but rather allows for releasing signaling molecules from the ECM, transsynaptic proteins, and latent form of growth factors. Notably, there are also indications implying those enzymes in the major neuropsychiatric disorders, probably by contributing to synaptic aberrations underlying such diseases as schizophrenia, bipolar, autism spectrum disorders, and drug addiction.

Original languageEnglish (US)
Pages (from-to)135-157
Number of pages23
JournalProgress in Brain Research
StatePublished - Jan 1 2014


  • Addiction
  • Autism
  • Cognitive behavior
  • Extracellular matrix
  • Long-term potentiation
  • Metalloproteinases
  • Schizophrenia
  • Thrombin
  • Trypsin

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