D'Antoni Simona, Spatuzza Michela, Bonaccorso Carmela M, Musumeci Sebastiano A, Ciranna Lucia, Nicoletti Ferdinando, Huber Kimberly M, Catania Maria Vincenza
Institute of Neurological Sciences, the National Research Council of Italy (CNR), Catania, Italy.
IRCCS Oasi Maria SS, Troina (EN), Italy.
Neurosci Biobehav Rev. 2014 Oct;46 Pt 2(Pt 2):228-41. doi: 10.1016/j.neubiorev.2014.02.003. Epub 2014 Feb 15.
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.
I 型代谢型谷氨酸受体（mGlu1 和 mGlu5）的激活会触发神经元和神经胶质细胞中的多种信号通路，这些信号通路在突触可塑性中有着不同的作用。最早以及许多关键研究在脆性 X 综合征（FXS）小鼠模型中发现了 mGlu5 受体功能异常，这促使了近期的研究发现 mGlu5 受体功能障碍存在于诸如智力障碍（ID）、强迫症（OCD）和自闭症等相关疾病中。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，许多研究聚焦于 mGlu5 信号传导对突触蛋白合成的失调。然而，新出现的证据发现，在 FXS 中 mGlu5 受体与其支架蛋白的相互作用异常，这导致了 mGlu5 受体功能障碍和与蛋白合成信号传导无关的表型。最后，mGlu5 功能的增强和减弱似乎都与 ID 和自闭症谱系障碍有关，这对这些发育障碍的潜在治疗有着重要影响。
