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首页> 外文期刊>The European Journal of Neuroscience >The molecular interplay between endocannabinoid and neurotrophin signals in the nervous system and beyond
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The molecular interplay between endocannabinoid and neurotrophin signals in the nervous system and beyond

机译：内源性大麻素和神经营养蛋白信号在神经系统内外的分子相互作用

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Neurotrophins are traditionally known for their roles in neuronal development, function and survival. More recent data has highlighted the importance of neurotrophin signalling in adult signalling contexts, including the regulation of synaptic transmission. In addition, neurotrophin levels are increased in inflammatory and neuropathic pain leading to sensitization to painful stimuli. Endocannabinoid (eCB) signalling was initially studied in the context of synaptic transmission and pain alleviation whilst recently gaining attention due to its involvement in the development of the nervous system. Similar to neurotrophins, eCB levels also rise during pain perception but result in diminished pain sensations. The overlap of cellular functions between neurotrophins and eCB signalling leads to the hypothesis that these signalling systems are positioned to regulate each other and narrow the multitude of actions that both systems can promote to the specific need of the cell. Therefore, in this review, we examine to what extent the involvement of these two signalling systems is co-ordinated as opposed to being coincidental, and causal to neuronal circuit modifications in pain. Available data point to numerous direct molecular interactions between the neurotrophin and eCB signalling systems in developmental and adult contexts, including receptor-level interplay, transcriptional control and synergistic regulation of downstream signalling cascades. Although experimental observations specifically in pain circuits are limited, the universality of downstream signalling systems from both neurotrophin and endocannabinoid receptors suggest an interdependent relationship between these two diverse signalling systems.
机译：传统上，神经营养蛋白因其在神经元发育，功能和存活中的作用而闻名。最近的数据强调了神经营养蛋白信号在成人信号传导环境中的重要性，包括突触传递的调节。另外，在炎性和神经性疼痛中神经营养蛋白水平升高，导致对疼痛刺激敏感。内源性大麻素（eCB）信号最初是在突触传递和疼痛缓解的背景下进行研究的，而最近由于其参与神经系统的发育而受到关注。与神经营养蛋白相似，eCB水平在疼痛感知过程中也会升高，但会导致疼痛感减弱。神经营养蛋白和eCB信号传导之间细胞功能的重叠导致了这样一个假设：这些信号传导系统的位置相互调节，并使两种系统都可以促进针对细胞特定需求的多种作用变窄。因此，在这篇综述中，我们研究了这两个信号系统的参与在多大程度上被协调，而不是巧合，并且是疼痛中神经元回路改变的原因。可获得的数据表明，在发育和成年背景下，神经营养蛋白和eCB信号系统之间存在许多直接的分子相互作用，包括受体水平的相互作用，转录控制和下游信号级联的协同调节。尽管具体在疼痛回路中的实验观察是有限的，但是来自神经营养蛋白和内源性大麻素受体的下游信号系统的普遍性提示这两种不同信号系统之间存在相互依存的关系。

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