Does the MK2-dependent production of TNFα regulate mGluR-dependent synaptic plasticity?

Abstract

The molecular mechanisms and signalling cascades that trigger the induction of group I metabotropic glutamate receptor (GI-mGluR)-dependent long-term depression (LTD) have been the subject of intensive investigation for nearly two decades. The generation of genetically modified animals has played a crucial role in elucidating the involvement of key molecules regulating the induction and maintenance of mGluR-LTD. In this review we will discuss the requirement of the newly discovered MAPKAPK-2 (MK2) and MAPKAPK-3 (MK3) signalling cascade in regulating GI-mGluR-LTD. Recently, it has been shown that the absence of MK2 impaired the induction of GI-mGluR-dependent LTD, an effect that is caused by reduced internalization of AMPA receptors (AMPAR). As the MK2 cascade directly regulates tumour necrosis factor alpha (TNFα) production, this review will examine the evidence that the release of TNFα acts to regulate glutamate receptor expression and therefore may play a functional role in the impairment of GI-mGluRdependent LTD and the cognitive deficits observed in MK2/3 double knockout animals. The strong links of increased TNFα production in both aging and neurodegenerative disease could implicate the action of MK2 in these processes.

Publication DOI: https://doi.org/10.2174/1570159X13666150624165939
Divisions: College of Health & Life Sciences > Aston Medical School
Additional Information: Published in Current Neuropharmacology
Uncontrolled Keywords: AMPAR trafficking,cognition,GI-mGluR-LTD,hippocampus,MK2,p38 MAPK,TNFα
Publication ISSN: 1875-6190
Last Modified: 10 Dec 2024 08:08
Date Deposited: 29 Jun 2016 12:20
Full Text Link: http://www.eure ... /132429/article
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PURE Output Type: Article
Published Date: 2016-07-01
Accepted Date: 2016-05-26
Authors: Hogg, Ellen L.
Müller, Jürgen
Corrêa, Sônia A.L.

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