How does angiotensin AT(2) receptor activation help neuronal differentiation and improve neuronal pathological situations?
How does angiotensin AT(2) receptor activation help neuronal differentiation and improve neuronal pathological situations?
复制标题
（2）受体激活的血管紧张素如何帮助神经元分化并改善神经元病理状况？
DOI：
10.3389/fendo.2012.00164
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发表时间：
2012
影响因子：
5.2
通讯作者：
Gallo-Payet N
中科院分区：
文献类型：
--
作者：
Guimond MO;Gallo-Payet N
血管紧张素II的血管紧张素2型（AT2）受体长期以来被认为仅限于少数组织，主要作用是抵消血管紧张素1型（AT1）受体。在神经元细胞中的功能研究已经证明了AT 2受体调节神经元兴奋性、神经突伸长和神经元迁移的能力，这表明它可能是脑功能的重要调节器。AT2受体在涉及学习和记忆的脑区表达的观察结果导致了它也可能涉及认知功能的假设。然而，将信号传导途径与生理效应联系起来一直被证明是具有挑战性的，因为与其生理功能相关的信息主要来自间接观察，无论是来自AT 1受体的阻断还是通过使用转基因动物。从机制的角度来看，与AT 2受体刺激相关的主要细胞内途径包括通过激活激酶和磷酸酶或产生一氧化氮和cGMP来调节磷酸化，其中一些与Gi偶联蛋白相关。该受体还可以与其他受体相互作用，或者与G蛋白偶联的受体如缓激肽，或者与生长因子受体如神经生长因子或血小板衍生生长因子受体相互作用。最近，新的进展也导致了各种伴侣蛋白的鉴定，从而为这种受体的作用机制提供了新的见解。本文综述了近年来有关神经细胞中AT 2受体诱导的信号通路的研究进展，并讨论了这种神秘受体的中枢作用的潜在治疗意义。特别是，我们强调的可能性，选择性AT2受体激活的非肽和选择性激动剂可能代表新的药理学工具，可能有助于改善受损的认知功能在阿尔茨海默病和其他神经认知障碍。
The angiotensin type 2 (AT2) receptor of angiotensin II has long been thought to be limited to few tissues, with the primary effect of counteracting the angiotensin type 1 (AT1) receptor. Functional studies in neuronal cells have demonstrated AT2 receptor capability to modulate neuronal excitability, neurite elongation, and neuronal migration, suggesting that it may be an important regulator of brain functions. The observation that the AT2 receptor was expressed in brain areas implicated in learning and memory led to the hypothesis that it may also be implicated in cognitive functions. However, linking signaling pathways to physiological effects has always proven challenging since information relative to its physiological functions has mainly emerged from indirect observations, either from the blockade of the AT1 receptor or through the use of transgenic animals. From a mechanistic standpoint, the main intracellular pathways linked to AT2 receptor stimulation include modulation of phosphorylation by activation of kinases and phosphatases or the production of nitric oxide and cGMP, some of which are associated with the Gi-coupling protein. The receptor can also interact with other receptors, either G protein-coupled such as bradykinin, or growth factor receptors such as nerve growth factor or platelet-derived growth factor receptors. More recently, new advances have also led to identification of various partner proteins, thus providing new insights into this receptor’s mechanism of action. This review summarizes the recent advances regarding the signaling pathways induced by the AT2 receptor in neuronal cells, and discussed the potential therapeutic relevance of central actions of this enigmatic receptor. In particular, we highlight the possibility that selective AT2 receptor activation by non-peptide and selective agonists could represent new pharmacological tools that may help to improve impaired cognitive performance in Alzheimer’s disease and other neurological cognitive disorders.