Autism spectrum disorders (ASDs) are neurodevelopmental disorders characterized by impaired social interaction and stereotyped behaviours. Increasing evidence suggests that a convergence on signaling pathways involved in protein translation and triggered by the activation of group I metabotropic glutamate (mGlu) receptors can be common to different ASDs. A dysregulation of mGlu5 receptor-mediated signaling has been reported in different animal models of ASD, including animal models of Fragile X syndrome (FXS) and Angelman Syndrome (AS). In this context, we have found that the interaction between mGlu5 receptor and its scaffolding protein Homer is abnormal in mouse models of FXS and AS (Giuffrida et al., J. Neurosci., 2005; Pignatelli et al., J. Neurosci, 2014). Thus, we are currently investigating if mGlu5 alteration is involved in other neurodevelopmental disorders associated with intellectual disability and Autism, such as Tuberous Sclerosis Complex (TSC) and Down Syndrome (DS). To this aim, we have studied protein expression of mGlu5 receptor and its endogenous regulators of cell surface localization, intracellular trafficking and signaling, such as Homer, Preso1, Tamalin and Norbin, on brain tissue of patients affected by these different pathologies. We have found a different pattern of expression of these proteins in these different pathologies. We observed that mGlu5 receptor, Homer1bc and Tamalin levels are increased in neurons of TSC patients, whereas a reduction is detected in Preso1 and Norbin levels. No difference was observed in mGlu5 receptor expression levels of AS patients; in contrast, a reduction is shown in Homer1bc levels. In addition, our data highlighted a reduction of Homer1bc and mGlu5 receptor in neurons of DS patients. Our findings provide strong support for the hypothesis that alteration in mGlu5 receptor expression is common to different ASDs and that a dysregulation of its regulatory proteins might have possible consequences for its activity.
Altered expression of mGlu5 receptor and its regulatory proteins in several Autism Spectrum Disorders.
S D'ANTONI;M CATANIA
2018
Abstract
Autism spectrum disorders (ASDs) are neurodevelopmental disorders characterized by impaired social interaction and stereotyped behaviours. Increasing evidence suggests that a convergence on signaling pathways involved in protein translation and triggered by the activation of group I metabotropic glutamate (mGlu) receptors can be common to different ASDs. A dysregulation of mGlu5 receptor-mediated signaling has been reported in different animal models of ASD, including animal models of Fragile X syndrome (FXS) and Angelman Syndrome (AS). In this context, we have found that the interaction between mGlu5 receptor and its scaffolding protein Homer is abnormal in mouse models of FXS and AS (Giuffrida et al., J. Neurosci., 2005; Pignatelli et al., J. Neurosci, 2014). Thus, we are currently investigating if mGlu5 alteration is involved in other neurodevelopmental disorders associated with intellectual disability and Autism, such as Tuberous Sclerosis Complex (TSC) and Down Syndrome (DS). To this aim, we have studied protein expression of mGlu5 receptor and its endogenous regulators of cell surface localization, intracellular trafficking and signaling, such as Homer, Preso1, Tamalin and Norbin, on brain tissue of patients affected by these different pathologies. We have found a different pattern of expression of these proteins in these different pathologies. We observed that mGlu5 receptor, Homer1bc and Tamalin levels are increased in neurons of TSC patients, whereas a reduction is detected in Preso1 and Norbin levels. No difference was observed in mGlu5 receptor expression levels of AS patients; in contrast, a reduction is shown in Homer1bc levels. In addition, our data highlighted a reduction of Homer1bc and mGlu5 receptor in neurons of DS patients. Our findings provide strong support for the hypothesis that alteration in mGlu5 receptor expression is common to different ASDs and that a dysregulation of its regulatory proteins might have possible consequences for its activity.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
