Pyruvate dehydrogenase kinases in the nervous system: Their principal functions in neuronal-glial metabolic interaction and neuro-metabolic disorders

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.