Pyruvate Dehydrogenase Kinases in the Nervous System: Their Principal Functions in Neuronal-glial Metabolic Interaction and Neuro-metabolic Disorders
Pyruvate Dehydrogenase Kinases in the Nervous System: Their Principal Functions in Neuronal-glial Metabolic Interaction and Neuro-metabolic Disorders
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DOI：
10.2174/157015912804143586
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发表时间：
2012-12-01
影响因子：
5.3
通讯作者：
Suk, Kyoungho
中科院分区：
文献类型：
--
作者：
Jha, Mithilesh Kumar;Jeon, Sangmin;Suk, Kyoungho
新陈代谢直接或间接参与活细胞中进行的所有过程。大脑通常被视为神经元-胶质复合体，其大部分能量来自葡萄糖的氧依赖性代谢，而线粒体丙酮酸脱氢酶复合体（PDC）在葡萄糖氧化过程中发挥着关键的调节作用。丙酮酸脱氢酶激酶（也称为 PDC 激酶或 PDK）是一种通过关闭 PDC 来调节葡萄糖代谢的激酶。已鉴定出四种具有组织特异性活性的 PDK 亚型。神经元和神经胶质细胞，特别是星形胶质细胞的代谢是相互关联的，并且这些细胞以整合的方式发挥功能。神经元和星形胶质细胞之间的能量耦合对于有效满足大脑的能量需求至关重要。越来越多的证据表明，PDK 和/或神经元-星形胶质细胞代谢相互作用的改变与多种神经系统疾病的发生有关。在这里，作者回顾了最近的研究成果，这些研究成果揭示了 PDK 在神经系统中的功能，特别是在神经元-胶质细胞代谢相互作用和神经代谢紊乱方面。
Metabolism is involved directly or indirectly in all processes conducted in living cells. The brain, popularly viewed as a neuronal-glial complex, gets most of its energy from the oxygen-dependent metabolism of glucose, and the mitochondrial pyruvate dehydrogenase complex (PDC) plays a key regulatory role during the oxidation of glucose. Pyruvate dehydrogenase kinase (also called PDC kinase or PDK) is a kinase that regulates glucose metabolism by switching off PDC. Four isoforms of PDKs with tissue specific activities have been identified. The metabolisms of neurons and glial cells, especially, those of astroglial cells, are interrelated, and these cells function in an integrated fashion. The energetic coupling between neuronal and astroglial cells is essential to meet the energy requirements of the brain in an efficient way. Accumulating evidence suggests that alterations in the PDKs and/or neuron-astroglia metabolic interactions are associated with the development of several neurological disorders. Here, the authors review the results of recent research efforts that have shed light on the functions of PDKs in the nervous system, particularly on neuron-glia metabolic interactions and neuro-metabolic disorders.