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The mGluR Theory of Fragile X Syndrome 

The mGluR Theory of Fragile X Syndrome
The mGluR Theory of Fragile X Syndrome

Dilja D. Krueger

and Mark F. Bear

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date: 12 July 2020

Fragile X Syndrome (FXS) is a single-gene disorder associated with mental retardation and autism that is caused by loss of expression of the fragile X mental retardation protein (FMRP). The “mGluR theory of fragile X” postulates that FMRP and group I metabotropic glutamate receptors (mGluRs) act in functional opposition to regulate protein synthesis at the synapse, with mGluRs activating and FMRP repressing translation of FMRP target mRNAs. This chapter first briefly introduces FMRP and metabotropic glutamate receptors. It reviews the current state of knowledge on the mGluR theory at the level of basic, preclinical, and clinical research. It then discusses the questions that remain to be addressed to ensure that pharmacological interventions based on the mGluR theory have the greatest possible chance of succeeding in clinical trials and providing safe and effective treatments for patients with FXS.

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