AFQ056, a new mGluR5 antagonist for treatment of fragile X syndrome
Levenga, Josien and de Vrij, Femke M.S. and van der Linde, Herma C. and Buijsen, Ronald A.M. and Nelson, David L. and Oostra, Ben A. and Koekkoek, Sebastiaan K. and Hayashi, Shigemi and Song, Cheng and Gomez-Mancilla, Baltazar and Gasparini, Fabrizio and Willemsen, Rob and Pop, Andreea S. and Nieuwenhuizen, Ingeborg (2011) AFQ056, a new mGluR5 antagonist for treatment of fragile X syndrome. Neurobiology of Disease. ISSN 0969-9961Full text not available from this repository.
Fragile X syndrome, the most common form of inherited intellectual disability, is caused by a lack of FMRP, which is the product of the Fmr1 gene. FMRP is an RNA-binding protein and a component of RNA-granules found in the dendrites of neurons. At the synapse, FMRP is involved in regulation of translation of specific target mRNAs upon stimulation of mGluR5 receptors.
In this study, we test the effects of a new mGluR5 antagonist (AFQ056) on the prepulse inhibition of startle response in mice. We show that Fmr1 KO mice have a deficit in inhibition of the startle response after a prepulse and that AFQ056 can rescue this phenotype. We also studied the effect of AFQ056 on cultured Fmr1 KO hippocampal neurons; untreated neurons showed elongated spines and treatment resulted in shortened spines. These results suggest that AFQ056 might be a potent mGluR5 antagonist to rescue various aspects of the fragile X phenotype.
|Additional Information:||author can archive post-print (ie final draft post-refereeing); Publisher's version/PDF cannot be used|
|Keywords:||Fragile X; mGluR5 antagonist; Pre-pulse inhibition; Eye blink conditioning|
|Date Deposited:||01 Apr 2011 23:45|
|Last Modified:||31 Jan 2013 00:45|