Role of protein kinase A in regulating mitochondrial function and neuronal development: implications to neurodegenerative diseases.

Role of protein kinase A in regulating mitochondrial function and neuronal development: implications to neurodegenerative diseases.
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DOI:
10.1515/revneuro-2014-0085
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发表时间:
2015
影响因子:
4.1
通讯作者:
Das Banerjee T
Das Banerjee T
中科院分区:
医学3区
文献类型:
--
作者:
Dagda RK;Das Banerjee T

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在神经元中,增强的PKA信号可提高突触的可塑性,促进神经元的发育,并增加多巴胺的合成。另一方面,PKA信号的减弱导致了包括阿尔茨海默病和帕金森病在内的多种脑退行性疾病的发生,这表明PKA主要起到神经保护作用。A-激酶锚定蛋白(AKAP)是一种以PKA和其他信号分子为靶点,定位于不同的亚细胞位置,将PKA信号定位于树突、树突棘、胞浆和轴突的大型多域支架蛋白。通过与三种不同的AKAP结合,PKA可以被募集到线粒体外膜,从而调节线粒体的动力学、结构、线粒体呼吸、运输、树突形态和神经元存活。在这篇综述中,我们综述了PKA调节的各种基本神经功能,但特别强调线粒体定位的PKA。最后,我们提供了PKA信号丢失如何在几种脑退行性疾病的病因中起作用的最新概述。
In neurons, enhanced PKA signaling elevates synaptic plasticity, promotes neuronal development, and increases dopamine synthesis. On the other hand, a decline in PKA signaling contributes to the etiology of several brain degenerative diseases including Alzheimer’s disease and Parkinson’s disease suggesting that PKA predominantly plays a neuroprotective role. A-kinase anchoring proteins (AKAP) are large multi-domain scaffold proteins that target PKA and other signaling molecules to distinct subcellular sites to strategically localize PKA signaling at dendrites, dendritic spines, cytosol, and axons. PKA can be recruited to outer mitochondrial membrane by associating with three different AKAPs to regulate mitochondrial dynamics, structure, mitochondrial respiration, trafficking, dendrite morphology, and neuronal survival. In this review, we survey the myriad of essential neuronal functions modulated by PKA but place a special emphasis on mitochondrially-localized PKA. Finally, we offer an updated overview of how loss of PKA signaling contributes to the etiology of several brain degenerative diseases.
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