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Glutamate receptor dysfunction and drug targets across models of autism spectrum disorders

机译:自闭症谱系障碍模型中的谷氨酸受体功能障碍和药物靶向

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摘要

There is strong evidence that metabotropic and ionotropic glutamate receptors are affected in autism spectrum disorders (ASD), but there are few candidate genes indicating involvement of these receptors. This suggests that glutamate receptor dysregulation may primarily be involved in the expression of ASD, but is an uncommon etiology. Directly implicated in models of fragile-X with ASD phenotypes is metabotropic glutamate receptor type 5 (mGluR5), which appears to be an effective pharmacologic target in a number of models of ASD. The review of other ASD models demonstrates that there is also evidence of a role for kainate, NMDA, and AMPA receptors in the neuropathophysiology of ASD, though the relationship between dysfunction in those receptors and ASD-associated phenotypes is not well understood. Current models indicate a way forward to delineate the role of glutamate receptors in ASD. Further development of preclinical models focusing on glutamate receptors may provide tools to target a clinically important subset of ASD symptoms.
机译:有强有力的证据表明,代谢型和离子型谷氨酸受体在自闭症谱系障碍(ASD)中受到影响,但几乎没有候选基因表明这些受体参与其中。这表明谷氨酸受体失调可能主要与ASD的表达有关,但这是一种罕见的病因。与易感性X型具有ASD表型直接相关的是5型代谢型谷氨酸受体(mGluR5),它似乎是许多ASD模型中的有效药理靶标。对其他ASD模型的审查表明,尽管尚不清楚这些受体的功能障碍与ASD相关表型之间的关系,但也有证据表明海藻酸盐,NMDA和AMPA受体在ASD的神经病理生理中起作用。当前的模型表明了描述谷氨酸受体在ASD中的作用的前进方法。着眼于谷氨酸受体的临床前模型的进一步发展可能提供针对ASD症状临床重要子集的工具。

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