INVOLVEMENT OF GROPU-I METABOTROPIC GLUTAMATE RECEPTORS IN THE PATHOPHYSIOLOGY OF FRAGILE X SYNDROME

Fragile X syndrome (FRAX) is a hereditary disease characterized by mental retardation, epilepsy, behavioural disorders, autisms, facial dysmorfisms and macroorchidism and a common cause of genetic mental retardation. It is caused by a gene defect that impairs the production of FRAX mental retardation protein (FMRP), which negatively regulates protein synthesis. The function of FMRP has been partially elucidated, but the mechanisms underlying cerebral dysfunctions in FRAX are unknown. The lack of FMRP might interfere with neuronal plasticity, the ability of neurons to modify their morphology and function following an external stimulus, which is believed to underlie cognitive functions. This project is aimed at studying the role that a group of receptors for neurotransmitters (mGlu receptors) may play in FRAX. These receptors are involved in neuronal plasticity and the biochemical mechanisms triggered by their activation might be altered in FRAX, because drugs that block their activity ameliorate certain pathological features of the disease. Our study will lead to the identification of biochemical mechanisms which are altered in the brain of FRAX patients and will therefore be helpful for a better understanding of the pathogenesis of this important developmental disorder. The obtained results will be important for developing new selective therapeutical strategies for FRAX patients.