Loss of the fragile X mental retardation protein decouples metabotropic glutamate receptor dependent priming of long-term potentiation from protein synthesis.

ABSTRACT: Fragile X Syndrome (FXS), the most common inherited form of intellectual disability, is caused by loss of the fragile X mental retardation protein (FMRP). FMRP is a negative regulator of local mRNA translation downstream of group 1 metabotropic glutamate receptor (Gp1 mGluR) activation. In the absence of FMRP there is excessive mGluR-dependent protein synthesis, resulting in exaggerated mGluR-dependent long-term synaptic depression (LTD) in area CA1 of the hippocampus. Understanding disease pathophysiology is critical for development of therapies for FXS and the question arises of whether it is more appropriate to target excessive LTD or excessive mGluR-dependent protein synthesis. Priming of long-term potentiation (LTP) is a qualitatively different functional consequence of Gp1 mGluR-stim

SUBMITTER: Auerbach BD 

PROVIDER: S-EPMC2934918 | biostudies-literature | 2010 Aug

REPOSITORIES: biostudies-literature