The role of nuclear Ca2+ in maintaining neuronal homeostasis and brain health.
The role of nuclear Ca2+ in maintaining neuronal homeostasis and brain health.
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DOI：
10.1242/jcs.254904
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发表时间：
2021-04
影响因子：
4
通讯作者：
P. Mozolewski;Maciej Jeziorek;C. Schuster;H. Bading;Bess Frost;Radek Dobrowolski
中科院分区：
文献类型：
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作者：
P. Mozolewski;Maciej Jeziorek;C. Schuster;H. Bading;Bess Frost;Radek Dobrowolski
细胞核内Ca 2+是神经元突触与细胞核之间对话的最有效介质之一，它调节异染色质状态、转录因子活性、细胞核形态和突触活动诱导的神经元基因表达。最近的研究强调了核Ca2+信号在持久的、活动诱导的适应和维持适当脑功能中的重要性。不同形式的神经适应需要瞬时核Ca2+信号传导和环AMP反应元件结合蛋白（CREB 1，这里称为CREB）作为其主要靶点，其作为可调开关驱动和调节与记忆，疼痛，成瘾和神经保护相关的特定基因表达谱。此外，核Ca 2+水平的降低已被证明是神经毒性的，并且是驱动神经退行性疾病进展以及影响神经元自噬的因果因素。由于其在大脑中的中心作用，核Ca2+信号传导的缺陷可能是衰老大脑中神经保护持续丧失的基础，从而导致阿尔茨海默病的病理生理学。在这篇综述中，我们讨论了“核钙假说”在人脑功能及其在控制不同形式的神经适应和神经保护中的作用的背景下的原则。此外，我们提出了最相关和最有前途的未来研究的前景。
Nuclear Ca2+ has emerged as one of the most potent mediators of the dialogue between neuronal synapses and the nucleus that regulates heterochromatin states, transcription factor activity, nuclear morphology and neuronal gene expression induced by synaptic activity. Recent studies underline the importance of nuclear Ca2+ signaling in long-lasting, activity-induced adaptation and maintenance of proper brain function. Diverse forms of neuroadaptation require transient nuclear Ca2+ signaling and cyclic AMP-responsive element-binding protein (CREB1, referred to here as CREB) as its prime target, which works as a tunable switch to drive and modulate specific gene expression profiles associated with memory, pain, addiction and neuroprotection. Furthermore, a reduction of nuclear Ca2+ levels has been shown to be neurotoxic and a causal factor driving the progression of neurodegenerative disorders, as well as affecting neuronal autophagy. Because of its central role in the brain, deficits in nuclear Ca2+ signaling may underlie a continuous loss of neuroprotection in the aging brain, contributing to the pathophysiology of Alzheimer's disease. In this Review, we discuss the principles of the 'nuclear calcium hypothesis' in the context of human brain function and its role in controlling diverse forms of neuroadaptation and neuroprotection. Furthermore, we present the most relevant and promising perspectives for future studies.