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.