Dysregulation of group-I metabotropic glutamate (mGlu) receptor mediated signalling in disorders associated with Intellectual Disability and Autism.
Dysregulation of group-I metabotropic glutamate (mGlu) receptor mediated signalling in disorders associated with Intellectual Disability and Autism.
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DOI：
10.1016/j.neubiorev.2014.02.003
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发表时间：
2014-10
影响因子：
8.2
通讯作者：
Catania MV
中科院分区：
文献类型：
--
作者：
D'Antoni S;Spatuzza M;Bonaccorso CM;Musumeci SA;Ciranna L;Nicoletti F;Huber KM;Catania MV
I组代谢性谷氨酸受体mGlu1和mGlu5的激活在神经元和神经胶质细胞中触发了不同的信号通路，这些信号通路与突触可塑性有关。最早也是最重要的研究发现，脆性X综合征(FXS)小鼠模型中mGlu5受体功能异常，这推动了最近的工作，发现mGlu5受体功能障碍与智能障碍(ID)、强迫症(OCD)和自闭症等相关疾病有关。因此，mGlu1/5受体功能障碍可能是这些复杂疾病的共同病因。此外，许多研究都集中在mGlu5信号对突触蛋白合成的失调。然而，新的证据发现在FXS中mGlu5受体与其支架蛋白的异常相互作用导致mGlu5受体功能障碍和表型独立于蛋白质合成的信号。最后，mGlu5功能增强和降低似乎都与ID和自闭症谱系障碍有关，对这些发育障碍的潜在治疗具有重要后果。
Activation of group-I metabotropic glutamate receptors, mGlu1 and mGlu5, triggers a variety of signalling pathways in neurons and glial cells, which are differently implicated in synaptic plasticity. The earliest and much of key studies discovered abnormal mGlu5 receptor function in Fragile X syndrome (FXS) mouse models which then motivated more recent work that finds mGlu5 receptor dysfunction in related disorders such as intellectual disability (ID), obsessive-compulsive disorder (OCD) and autism. Therefore, mGlu1/5 receptor dysfunction may represent a common aetiology of these complex diseases. Furthermore, many studies have focused on dysregulation of mGlu5 signalling to synaptic protein synthesis. However, emerging evidence finds abnormal mGlu5 receptor interactions with its scaffolding proteins in FXS which results in mGlu5 receptor dysfunction and phenotypes independent of signalling to protein synthesis. Finally, both an increased and reduced mGlu5 functioning seem to be associated with ID and autism spectrum disorders, with important consequences for potential treatment of these developmental disorders.