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Title: | PDE inhibition in distinct cell types to reclaim the balance of synaptic plasticity | Authors: | ROMBAUT, Ben KESSELS, Sofie SCHEPERS, Melissa TIANE, Assia PAES, Dean Solomina, Yevgeniya PICCART, Elisabeth van den Hove, Daniel BRONE, Bert Prickaerts, Jos VANMIERLO, Tim |
Issue Date: | 2021 | Publisher: | IVYSPRING INT PUBL | Source: | Theranostics, 11 (5) , p. 2080 -2097 | Abstract: | Synapses are the functional units of the brain. They form specific contact points that drive neuronal communication and are highly plastic in their strength, density, and shape. A carefully orchestrated balance between synaptogenesis and synaptic pruning, i.e., the elimination of weak or redundant synapses, ensures adequate synaptic density. An imbalance between these two processes lies at the basis of multiple neuropathologies. Recent evidence has highlighted the importance of glia-neuron interactions in the synaptic unit, emphasized by glial phagocytosis of synapses and local excretion of inflammatory mediators. These findings warrant a closer look into the molecular basis of cell-signaling pathways in the different brain cells that are related to synaptic plasticity. In neurons, intracellular second messengers, such as cyclic guanosine or adenosine monophosphate (cGMP and cAMP, respectively), are known mediators of synaptic homeostasis and plasticity. Increased levels of these second messengers in glial cells slow down inflammation and neurodegenerative processes. These multi-faceted effects provide the opportunity to counteract excessive synapse loss by targeting cGMP and cAMP pathways in multiple cell types. Phosphodiesterases (PDEs) are specialized degraders of these second messengers, rendering them attractive targets to combat the detrimental effects of neurological disorders. Cellular and subcellular compartmentalization of the specific isoforms of PDEs leads to divergent downstream effects for these enzymes in the various central nervous system resident cell types. This review provides a detailed overview on the role of PDEs and their inhibition in the context of glia-neuron interactions in different neuropathologies characterized by synapse loss. In doing so, it provides a framework to support future research towards finding combinational therapy for specific neuropathologies. | Notes: | Vanmierlo, T (corresponding author), Hasselt Univ, Biomed Res Inst, Dept Neurosci, European Grad Sch Neurosci,UHasselt, Hasselt, Belgium.; Vanmierlo, T (corresponding author), Maastricht Univ, Dept Psychiat & Neuropsychol, Sch Mental Hlth & Neurosci, European Grad Sch Neurosci, Maastricht, Netherlands. tim.vanmierlo@uhasselt.be |
Other: | Vanmierlo, T (corresponding author), Hasselt Univ, Biomed Res Inst, Dept Neurosci, European Grad Sch Neurosci,UHasselt, Hasselt, Belgium. tim.vanmierlo@uhasselt.be | Keywords: | neurodegeneration;neurodegeneration;synapses;synapses;phosphodiesterase;phosphodiesterase;cell-signaling;cell-signaling;glia-neuron;glia-neuron | Document URI: | http://hdl.handle.net/1942/33485 | ISSN: | 1838-7640 | e-ISSN: | 1838-7640 | DOI: | 10.7150/thno.50701 | ISI #: | 000600556000007 | Rights: | The author(s). This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions. | Category: | A1 | Type: | Journal Contribution | Validations: | ecoom 2022 |
Appears in Collections: | Research publications |
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v11p2080.pdf | Published version | 784.68 kB | Adobe PDF | View/Open |
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