Program in Neurosciences & Mental Health, the Hospital for Sick Children, Toronto, ON, Canada.
FEBS J. 2012 Jan;279(1):2-11. doi: 10.1111/j.1742-4658.2011.08390.x. Epub 2011 Dec 5.
Upregulation of N-methyl-D-aspartate (NMDA) receptor function by the nonreceptor protein tyrosine kinase Src has been implicated in physiological plasticity at glutamatergic synapses. Here, we highlight recent findings suggesting that aberrant Src upregulation of NMDA receptors may also be key in pathophysiological conditions. Within the nociceptive processing network in the dorsal horn of the spinal cord, pathologically increased Src upregulation of NMDA receptors is critical for pain hypersensitivity in models of chronic inflammatory and neuropathic pain. On the other hand, in the hippocampus and prefrontal cortex, the physiological upregulation of NMDA receptors by Src is blocked by neuregulin 1-ErbB4 signaling, a pathway that is genetically implicated in the positive symptoms of schizophrenia. Thus, either over-upregulation or under-upregulation of NMDA receptors by Src may lead to pathological conditions in the central nervous system. Therefore, normalizing Src upregulation of NMDA receptors may be a novel therapeutic approach for central nervous system disorders, without the deleterious consequences of directly blocking NMDA receptors.
N-甲基-D-天冬氨酸（NMDA）受体功能的上调受非受体蛋白酪氨酸激酶Src 的影响，这与谷氨酸能突触的生理可塑性有关。在这里，我们强调了最近的发现，表明 NMDA 受体的异常 Src 上调也可能是病理生理条件的关键。在脊髓背角的伤害性处理网络中，病理性增加的 Src 对 NMDA 受体的上调对于慢性炎症和神经性疼痛模型中的痛觉过敏至关重要。另一方面，在海马体和前额叶皮层中，Src 通过神经调节蛋白 1-ErbB4 信号通路对 NMDA 受体的生理性上调被阻断，该通路在精神分裂症的阳性症状中具有遗传相关性。因此，Src 对 NMDA 受体的过度上调或下调都可能导致中枢神经系统出现病理状态。因此，正常化 Src 对 NMDA 受体的上调可能是一种治疗中枢神经系统疾病的新方法，而不会产生直接阻断 NMDA 受体的有害后果。
