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Reviews in the Neurosciences

Editor-in-Chief: Huston, Joseph P.

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Volume 24, Issue 4


Does extracellular proteolysis control mammalian cognition?

Hideki Tamura
  • Corresponding author
  • Laboratory of Functional Neuroscience, Graduate School of Biological Sciences, Nara Institute of Science and Technology, Ikoma, Nara 630–0192, Japan
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/ Yasuyuki Ishikawa
  • Department of Systems Life Engineering, Maebashi Institute of Technology, Maebashi, Gunma 371-0816, Japan
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/ Sadao Shiosaka
  • Corresponding author
  • Laboratory of Functional Neuroscience, Graduate School of Biological Sciences, Nara Institute of Science and Technology, Ikoma, Nara 630–0192, Japan
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Published Online: 2013-05-15 | DOI: https://doi.org/10.1515/revneuro-2013-0007


Recent advances in neuroscience techniques for analyzing synaptic functions, have revealed that even in a fully developed nervous system, dynamic structural changes in synapses can modify a variety of interactions between the presynaptic and postsynaptic neuron. Accumulating evidence suggests that extracellular proteases are involved in the structural modification of synapses through various pathways, including proteolytic cleavage at specific amino acid residues of the extracellular matrix proteins, cell adhesion molecules, and neurotrophic factors. Limited proteolysis induces changes in the properties of substrate proteins or releases functional domains (such as ligands) of the substrate proteins, which activate a signal transduction cascade, and hence could serve to initiate a variety of physiological functions. Such morphological and functional synaptic plasticity might underlie cognitive processes, including learning and memory in animals and humans. Here, we review potential molecular mechanisms of cognition-related focal proteolysis in the hippocampus. In addition, we developed a novel screening method to identify the physiological substrate for proteases.

Keywords: hippocampus; learning and memory; long-term potentiation; matrix metalloproteinase; serine protease; synaptic plasticity


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About the article

Hideki Tamura

Hideki Tamura received MS and the PhD degrees from the Nara Institute of Science and Technology (NAIST), Japan, in 2003 and 2006, respectively. Since 2006, he has been Assistant Professor at NAIST. His current research interests include the neural basis of cognitive function and dysfunction.

Yasuyuki Ishikawa

Yasuyuki Ishikawa received MS and PhD degrees from Osaka University in 1998 and 2001, respectively. In 2003, he joined the Graduate School of Biological Sciences, Nara Institute of Science and Technology, Japan, as an Assistant Professor. He has been an Associated Professor in Maebashi Institute of Technology, since 2013. His research interest is learning and memory.

Sadao Shiosaka

Sadao Shiosaka received an MS degree from Nagoya University, Japan, in 1977 and a PhD degree from Osaka University, Japan, in 1982. In 1979, he joined the Department of Anatomy, Osaka University Medical School as Assistant Professor. He was appointed an Associated Professor in 1986. He is currently a Professor of Neuroscience at the Nara Institute of Science and Technology. His research interest is in activity-dependent synaptic plasticity via a local extracellular proteolytic activity at the synapse.

Corresponding authors: Hideki Tamura and Sadao Shiosaka, Laboratory of Functional Neuroscience, Graduate School of Biological Sciences, Nara Institute of Science and Technology, Ikoma, Nara 630–0192, Japan

Received: 2013-03-12

Accepted: 2013-04-14

Published Online: 2013-05-15

Published in Print: 2013-08-01

Citation Information: Reviews in the Neurosciences, Volume 24, Issue 4, Pages 365–374, ISSN (Online) 2191-0200, ISSN (Print) 0334-1763, DOI: https://doi.org/10.1515/revneuro-2013-0007.

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