title: The Role of Proteases in Hippocampal Synaptic Plasticity: Putting Together Small Pieces of a Complex Puzzle.
abstract: Long-term synaptic plasticity in the hippocampus is thought to underlie the formation of certain forms of memory, including spatial memory. The early phase of long-term synaptic potentiation and synaptic depression depends on post-translational modifications of synaptic proteins, while protein synthesis is also required for the late-phase of both forms of synaptic plasticity (L-LTP and L-LTD). Numerous pieces of evidence show a role for different types of proteases in synaptic plasticity, further increasing the diversity of mechanisms involved in the regulation of the intracellular and extracellular protein content. The cleavage of extracellular proteins is coupled to changes in postsynaptic intracellular mechanisms, and additional alterations in this compartment result from the protease-mediated targeting of intracellular proteins. Both mechanisms contribute to initiate signaling cascades that drive downstream pathways coupled to synaptic plasticity. In this review we summarize the evidence pointing to a role for extracellular and intracellular proteases, with distinct specificities, in synaptic plasticity. Where in the cells the proteases are located, and how they are regulated is also discussed. The combined actions of proteases and translation mechanisms contribute to a tight control of the synaptic proteome relevant for long-term synaptic potentiation and synaptic depression in the hippocampus. Additional studies are required to elucidate the mechanisms whereby these changes in the synaptic proteome are related with plasticity phenomena.
authors.affiliation: Faculty of Medicine (Polo I), Center for Neuroscience and Cell Biology, University of Coimbra, Rua Larga, 3004-504, Coimbra, Portugal.|Doctoral Programme in Experimental Biology and Biomedicine, Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504, Coimbra, Portugal.|Institute for Interdisciplinary Research (IIIUC), University of Coimbra, 3030-789, Coimbra, Portugal.
authors.forename: Ivan L
authors.initials: IL
authors.lastname: Salazar
authors.affiliation: Faculty of Medicine (Polo I), Center for Neuroscience and Cell Biology, University of Coimbra, Rua Larga, 3004-504, Coimbra, Portugal.|Institute for Interdisciplinary Research (IIIUC), University of Coimbra, 3030-789, Coimbra, Portugal.
authors.forename: Margarida V
authors.initials: MV
authors.lastname: Caldeira
authors.affiliation: Faculty of Medicine (Polo I), Center for Neuroscience and Cell Biology, University of Coimbra, Rua Larga, 3004-504, Coimbra, Portugal.|Laboratory for Axon Growth and Regeneration, German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.
authors.forename: Michele
authors.initials: M
authors.lastname: Curcio
authors.affiliation: Faculty of Medicine (Polo I), Center for Neuroscience and Cell Biology, University of Coimbra, Rua Larga, 3004-504, Coimbra, Portugal. cbduarte@ci.uc.pt.|Department of Life Sciences, University of Coimbra, 3000-456, Coimbra, Portugal. cbduarte@ci.uc.pt.
authors.forename: Carlos B
authors.initials: CB
authors.lastname: Duarte
mesh_terms: D000818:Animals; D006624:Hippocampus / Q000201:enzymology / Q000502:physiology*; D006801:Humans; D009473:Neuronal Plasticity; D010447:Peptide Hydrolases / Q000378:metabolism*; D059748:Proteolysis
chemical_list: D010447:Peptide Hydrolases
keywords: Calpains; Long-term synaptic depression (LTD); Long-term synaptic potentiation (LTP); Proteases; Proteasome; Tissue plasminogen activator (tPA)